Note: Descriptions are shown in the official language in which they were submitted.
METHODS AND COMPOSITIONS TO INCREASE HAIR GROWTH
AND/OR PREVENT HAIR LOSS
BACKGROUND
[0001] Dermatologists recognize many different types of hair loss, the most
common by far
being "androgenetic alopecia" wherein human males or females begin losing
scalp hair at the
temples and on the crown of the head. While this type of hair loss is largely
confined to males,
hence its common name "male pattern baldness," it is not unknown in women.
[0002] Androgenetic alopecia (AGA) is the most common form of hair loss,
affecting
approximately 50 percent of all men and women by the age of 50. Common
treatments for
androgenetic alopecia include hair follicle transplants, topical therapies,
and orally prescribed
anti-androgens. The hyperandrogenic stimulation that causes androgenetic
alopecia also
produces other undesirable physiological symptoms including acne vulgaris,
benign prostatic
hyperplasia, female hirsutism, and seborrhea.
[0003] Several anti-alopecia agents such as minoxidil and cyoctol have gained
attention.
However, these anti-alopecia agents are only minimally effective in some cases
and/or can
cause adverse dermatological or systemic reactions. In particular, single
agent formulations
may have limited efficacy in many subjects.
[0004] It is also known that many of the currently available formulations have
to be applied
topically two or more times in the course of a 24 hour period. The frequency
of application can
mitigate the efficacy of treatment due to missed applications and also lead to
user frustration
and/or error.
[0005] In addition, many conventional formulations have undesirable side
effects of drying hair
and/or scalp, frizzing or kinking of the hair, scalp itching or irritation and
undesirable cosmetic
effects such as slow drying upon application leading to an extended time
period of "wet" hair. An
important characteristic of a hair treatment formulation should be that it
provides not only
reduced hair loss and/or increased hair growth, but also healthy looking hair
and scalp.
[0006] Thus, despite advances in research directed to treat hair loss and/or
increase hair
growth, there is still a scarcity of topical treatment compositions and
methods that are potent,
efficacious, and require minimal frequency of application, while at the same
time minimizing
undesirable side-effects and providing healthy looking hair and/or scalp.
These needs and
other needs are satisfied by the present disclosure.
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Date Recue/Date Received 2023-08-18
SUMMARY
[0007] In accordance with the purpose(s) of the present disclosure, as
embodied and broadly
described herein, the disclosure, in one aspect, relates to topical
formulations, methods of
making same, and methods of treating hair loss using same.
[0008] In an aspect, the present disclosure pertains to topical formulations
for treatment of hair
loss and/or to increase hair growth, the formulation comprising: a therapeutic
composition
comprising therapeutically effective amounts of azelaic acid, minoxidil,
finasteride, and
dutasteride; and one or more compounding agents.
[0009] In a further aspect, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising therapeutically effective amounts of azelaic acid,
minoxidil, finasteride,
and dutasteride; one or more compounding agents; and optionally caffeine
and/or saw palmetto
extract.
[0010] In a further aspect, the present disclosure pertains to a method of
treating hair loss by
applying a disclosed topical formulation.
[0011] In a further aspect, the present disclosure pertains to a method of
enhancing hair grow
by applying a disclosed topical formulation.
[0012] Other systems, methods, features, and advantages of the present
disclosure will be or
become apparent to one with skill in the art upon examination of the following
drawings and
detailed description. It is intended that all such additional systems,
methods, features, and
advantages be included within this description, be within the scope of the
present disclosure,
and be protected by the accompanying claims. In addition, all optional and
preferred features
and modifications of the described aspects are usable in all aspects of the
disclosure taught
herein. Furthermore, the individual features of the dependent claims, as well
as all optional and
preferred features and modifications of the described aspects are combinable
and
interchangeable with one another.
[0013] Additional advantages of the disclosure will be set forth in part in
the description which
follows, and in part will be obvious from the description, or can be learned
by practice of the
disclosure. It is to be understood that both the foregoing general description
and the following
detailed description are exemplary and explanatory only and are not
restrictive of the disclosure,
as claimed.
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Date Recue/Date Received 2023-08-18
DETAILED DESCRIPTION
[0014] Many modifications and other aspects disclosed herein will come to mind
to one skilled
in the art to which the disclosed compositions and methods pertain having the
benefit of the
teachings presented in the foregoing descriptions and the associated drawings.
Therefore, it is
to be understood that the disclosures are not to be limited to the specific
aspects disclosed and
that modifications and other aspects are intended to be included within the
scope of the
appended claims. The skilled artisan will recognize many variants and
adaptations of the
aspects described herein.
[0015] Although specific terms are employed herein, they are used in a generic
and descriptive
sense only and not for purposes of limitation.
[0016] As will be apparent to those of skill in the art upon reading this
disclosure, each of the
individual aspects described and illustrated herein has discrete components
and features which
may be readily separated from or combined with the features of any of the
other several aspects
without departing from the scope or spirit of the present disclosure.
[0017] Any recited method can be carried out in the order of events recited or
in any other order
that is logically possible. That is, unless otherwise expressly stated, it is
in no way intended that
any method or aspect set forth herein be construed as requiring that its steps
be performed in a
specific order. Accordingly, where a method claim does not specifically state
in the claims or
descriptions that the steps are to be limited to a specific order, it is no
way intended that an
order be inferred, in any respect. This holds for any possible non-express
basis for
interpretation, including matters of logic with respect to arrangement of
steps or operational
flow, plain meaning derived from grammatical organization or punctuation, or
the number or
type of aspects described in the specification.
[0018] All publications mentioned herein disclose and describe the methods
and/or materials in
connection with which the publications are cited. The publications discussed
herein are
provided solely for their disclosure prior to the filing date of the present
application. Nothing
herein is to be construed as an admission that the present disclosure is not
entitled to antedate
such publication by virtue of prior disclosure. Further, the dates of
publication provided herein
can be different from the actual publication dates, which can require
independent confirmation.
[0019] While aspects of the present disclosure can be described and claimed in
a particular
statutory class, such as the system statutory class, this is for convenience
only and one of skill
in the art will understand that each aspect of the present disclosure can be
described and
3
Date Recue/Date Received 2023-08-18
claimed in any statutory class.
[0020] It is also to be understood that the terminology used herein is for the
purpose of
describing particular aspects only and is not intended to be limiting. Unless
defined otherwise,
all technical and scientific terms used herein have the same meaning as
commonly understood
by one of ordinary skill in the art to which the disclosed compositions and
methods belong. It will
be further understood that terms, such as those defined in commonly used
dictionaries, should
be interpreted as having a meaning that is consistent with their meaning in
the context of the
specification and relevant art and should not be interpreted in an idealized
or overly formal
sense unless expressly defined herein.
[0021] Prior to describing the various aspects of the present disclosure, the
following definitions
are provided and should be used unless otherwise indicated. Additional terms
may be defined
elsewhere in the present disclosure.
Definitions
[0022] As used herein, "comprising" is to be interpreted as specifying the
presence of the stated
features, integers, steps, or components as referred to, but does not preclude
the presence or
addition of one or more features, integers, steps, or components, or groups
thereof. Moreover,
each of the terms "by", "comprising," "comprises", "comprised of,"
"including," "includes,"
"included," "involving," "involves," "involved," and "such as" are used in
their open, non-limiting
sense and may be used interchangeably. Further, the term "comprising" is
intended to include
examples and aspects encompassed by the terms "consisting essentially of" and
"consisting of."
Similarly, the term "consisting essentially or is intended to include examples
encompassed by
the term "consisting of.
[0023] As used in the specification and the appended claims, the singular
forms "a," "an" and
"the" include plural referents unless the context clearly dictates otherwise.
Thus, for example,
reference to "a silicone base," "a gel base for gel-cream emulsions," or "a
heavy cream base,"
including, but not limited to, two or more such silicone bases, gel bases for
gel-cream
emulsions, or heavy cream base, and the like.
[0024] It should be noted that ratios, concentrations, amounts, and other
numerical data can be
expressed herein in a range format. It will be further understood that the
endpoints of each of
the ranges are significant both in relation to the other endpoint, and
independently of the other
endpoint. It is also understood that there are a number of values disclosed
herein, and that each
value is also herein disclosed as "about" that particular value in addition to
the value itself. For
4
Date Recue/Date Received 2023-08-18
example, if the value "10" is disclosed, then "about 10" is also disclosed.
Ranges can be
expressed herein as from "about" one particular value, and/or to "about"
another particular
value. Similarly, when values are expressed as approximations, by use of the
antecedent
"about," it will be understood that the particular value forms a further
aspect. For example, if the
value "about 10" is disclosed, then "10" is also disclosed.
[0025] When a range is expressed, a further aspect includes from the one
particular value
and/or to the other particular value. For example, where the stated range
includes one or both
of the limits, ranges excluding either or both of those included limits are
also included in the
disclosure, e.g. the phrase "x to y" includes the range from 'x' to 'y' as
well as the range greater
than 'x' and less than 'y'. The range can also be expressed as an upper limit,
e.g. 'about x, y, z,
or less' and should be interpreted to include the specific ranges of 'about
x', 'about y', and
'about z' as well as the ranges of 'less than x', less than y', and 'less than
z'. Likewise, the
phrase 'about x, y, z, or greater' should be interpreted to include the
specific ranges of 'about x',
'about y', and 'about z' as well as the ranges of 'greater than x', greater
than y', and 'greater
than z'. In addition, the phrase "about 'x' to y", where 'x' and 'y' are
numerical values, includes
"about 'x' to about 'y'".
[0026] It is to be understood that such a range format is used for convenience
and brevity, and
thus, should be interpreted in a flexible manner to include not only the
numerical values
explicitly recited as the limits of the range, but also to include all the
individual numerical values
or sub-ranges encompassed within that range as if each numerical value and sub-
range is
explicitly recited. To illustrate, a numerical range of "about 0.1% to 5%"
should be interpreted to
include not only the explicitly recited values of about 0.1% to about 5%, but
also include
individual values (e.g., about 1%, about 2%, about 3%, and about 4%) and the
sub-ranges (e.g.,
about 0.5% to about 1.1%; about 5% to about 2.4%; about 0.5% to about 3.2%,
and about 0.5%
to about 4.4%, and other possible sub-ranges) within the indicated range.
[0027] As used herein, the terms "about," "approximate," "at or about," and
"substantially" mean
that the amount or value in question can be the exact value or a value that
provides equivalent
results or effects as recited in the claims or taught herein. That is, it is
understood that amounts,
sizes, formulations, parameters, and other quantities and characteristics are
not and need not
be exact, but may be approximate and/or larger or smaller, as desired,
reflecting tolerances,
conversion factors, rounding off, measurement error and the like, and other
factors known to
those of skill in the art such that equivalent results or effects are
obtained. In some
circumstances, the value that provides equivalent results or effects cannot be
reasonably
Date Recue/Date Received 2023-08-18
determined. In such cases, it is generally understood, as used herein, that
"about" and "at or
about" mean the nominal value indicated 10% variation unless otherwise
indicated or inferred.
In general, an amount, size, formulation, parameter or other quantity or
characteristic is "about,"
"approximate," or "at or about" whether or not expressly stated to be such. It
is understood that
where "about," "approximate," or "at or about" is used before a quantitative
value, the parameter
also includes the specific quantitative value itself, unless specifically
stated otherwise.
[0028] As used herein, the term "effective amount" refers to an amount that is
sufficient to
achieve the desired modification of a physical property of the composition or
material. For
example, an "effective amount" of a therapeutic agent refers to an amount that
is sufficient to
achieve the desired improvement in clinical condition modulated by the
formulation component,
e.g. achieving the desired level of hair growth or mitigation of hair loss.
The specific level in
terms of wt% in a composition required as an effective amount will depend upon
a variety of
factors including the amount and type of therapeutic agent and formulation
type, e.g., ointment,
cream, gel, and the like.
[0029] As used herein, the terms "optional" or "optionally" means that the
subsequently
described event or circumstance can or cannot occur, and that the description
includes
instances where said event or circumstance occurs and instances where it does
not.
[0030] Therapeutic agents should be understood to include the neutral forms of
the drug and
pharmaceutically acceptable forms thereof. "Pharmaceutically acceptable"
refers to those
compounds, materials, compositions, salts and/or dosage forms which, within
the scope of
sound medical judgment, are suitable for administration to patients without
excessive toxicity,
irritation, allergic response, or other problems or complications commensurate
with a
reasonable benefit/risk ratio. By "pharmaceutically acceptable forms" thereof
is meant any
pharmaceutically acceptable derivative or variation, including stereoisomers,
stereoisomer
mixtures, enantiomers, solvates, hydrates, isomorphs, polymorphs,
pseudomorphs, salt forms
and prodrugs. Preferably in some aspects, the pharmaceutically acceptable
forms include salt
forms. In other preferable aspects the pharmaceutically acceptable forms
include, any
stereoisomer or stereoisomeric mixture of the therapeutic agent.
[0031] Unless otherwise specified, temperatures referred to herein are based
on atmospheric
pressure (i.e. one atmosphere).
Disclosed Formulations
[0032] In various aspects, the present disclosure pertains to topical
formulations for treatment
6
Date Recue/Date Received 2023-08-18
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising therapeutically effective amounts of azelaic acid,
minoxidil, finasteride,
and dutasteride; and one or more compounding agents. VVithout wishing to be
bound by a
particular theory, it is believed that the disclosed combination of azelaic
acid, minoxidil,
finasteride, and dutasteride in the disclosed amounts can have a synergistic
effect with regard
to increasing hair growth. Further, without wishing to be bound by a
particular theory, it is
believed that the disclosed combination of azelaic acid, minoxidil,
finasteride, and dutasteride in
the disclosed amounts can have a synergistic effect with regard to mitigating
or slowing hair
loss. As used herein, the cream base is inclusive of a heavy cream base. It is
understood that
terms such as "cream base," "heavy cream base," "a gel base for gel-cream
emulsions," and
"silicone base" are intended to be in the context of pharmaceutically
acceptable forms of a
cream base," "heavy cream base," "a gel base for gel-cream emulsions," and
"silicone base."
[0033] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents comprises therapeutically effective amounts of azelaic acid, minoxidil,
finasteride, and
dutasteride as follows: about 0.100 wt% to about 0.500 wt% azelaic acid; about
10 wt% to about
20 wt% minoxidil; about 0.05 wt% to about 0.50 wt% finasteride; and about
0.001 wt% to about
0.030 wt% dutasteride; wherein the wt% of a component is based on the total
weight of the
therapeutic composition; and one or more compound agents.
[0034] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents comprises therapeutically effective amounts of azelaic acid, minoxidil,
finasteride, and
dutasteride as follows: about 0.300 wt% to about 0.400 wt% azelaic acid; about
12 wt% to about
17 wt% minoxidil; about 0.10 wt% to about 0.30 wt% finasteride; and about
0.005 wt% to about
0.015 wt% dutasteride; wherein the wt% of a component is based on the total
weight of the
therapeutic composition; and one or more compounding agents.
[0035] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents comprises therapeutically effective amounts of azelaic acid, minoxidil,
finasteride, and
dutasteride as follows: about 0.325 wt% azelaic acid; about 15 wt% minoxidil;
about 0.20 wt%
finasteride; and about 0.010 wt% dutasteride; wherein the wt% of a component
is based on the
total weight of the therapeutic composition and one or more compounding
agents.
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Date Recue/Date Received 2023-08-18
[0036] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents comprises a therapeutically effective amount of azelaic acid, wherein
the azelaic acid is
present in an amount of about 0.100 wt%, about 0.105 wt%, about 0.110 wt%,
about 0.115 wt%,
about 0.120 wt%, about 0.125 wt%, about 0.130 wt%, about 0.135 wt%, about
0.140 wt%, about
0.145 wt%, about 0.150 wt%, about 0.155 wt%, about 0.160 wt%, about 0.165 wt%,
about 0.170
wt%, about 0.175 wt%, about 0.180 wt%, about 0.185 wt%, about 0.190 wt%, about
0.195 wt%,
about 0.200 wt%, about 0.205 wt%, about 0.210 wt%, about 0.215 wt%, about
0.220 wt%, about
0.225 wt%, about 0.230 wt%, about 0.235 wt%, about 0.240 wt%, about 0.245 wt%,
about 0.250
wt%, about 0.255 wt%, about 0.260 wt%, about 0.265 wt%, about 0.270 wt%, about
0.275 wt%,
about 0.280 wt%, about 0.285 wt%, about 0.290 wt%, about 0.295 wt%, about
0.300 wt%, about
0.305 wt%, about 0.310 wt%, about 0.315 wt%, about 0.320 wt%, about 0.325 wt%,
about 0.330
wt%, about 0.335 wt%, about 0.340 wt%, about 0.345 wt%, about 0.350 wt%, about
0.355 wt%,
about 0.360 wt%, about 0.365 wt%, about 0.370 wt%, about 0.375 wt%, about
0.380 wt%, about
0.385 wt%, about 0.390 wt%, about 0.395 wt%, about 0.400 wt%, about 0.405 wt%,
about 0.410
wt%, about 0.415 wt%, about 0.420 wt%, about 0.425 wt%, about 0.430 wt%, about
0.435 wt%,
about 0.440 wt%, about 0.445 wt%, about 0.450 wt%, about 0.455 wt%, about
0.460 wt%, about
0.465 wt%, about 0.470 wt%, about 0.475 wt%, about 0.480 wt%, about 0.485 wt%,
about 0.490
wt%, about 0.495 wt%, about 0.500 wt%; or any range encompassed by the
foregoing values;
or any combination of the foregoing values.
[0037] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents comprises therapeutically effective amounts of minoxidil, wherein the
minoxidil is present
in an amount of about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%,
about 1.4 wt%,
about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%,
about 2.0 wt%,
about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%,
about 2.6 wt%,
about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%,
about 3.2 wt%,
about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%,
about 3.8 wt%,
about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%,
about 4.4 wt%,
about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%,
about 5.0 wt%,
about 5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%,
about 5.6 wt%,
about 5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%,
about 6.2 wt%,
about 6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%,
about 6.8 wt%,
about 6.9 wt%, about 7.0 wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%,
about 7.4 wt%,
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Date Recue/Date Received 2023-08-18
about 7.5 wt%, about 7.6 wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%,
about 8.0 wt%,
about 8.1 wt%, about 8.2 wt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%,
about 8.6 wt%,
about 8.7 wt%, about 8.8 wt%, about 8.9 wt%, about 9.0 wt%, about 9.1 wt%,
about 9.2 wt%,
about 9.3 wt%, about 9.4 wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%,
about 9.8 wt%,
about 9.9 wt%, about 10.0 wt%, about 10.1 wt%, about 10.2 wt%, about 10.3 wt%,
about 10.4
wt%, about 10.5 wt%, about 10.6 wt%, about 10.7 wt%, about 10.8 wt%, about
10.9 wt%, about
11.0 wt%, about 11.1 wt%, about 11.2 wt%, about 11.3 wt%, about 11.4 wt%,
about 11.5 wt%,
about 11.6 wt%, about 11.7 wt%, about 11.8 wt%, about 11.9 wt%, about 12.0
wt%, about 12.1
wt%, about 12.2 wt%, about 12.3 wt%, about 12.4 wt%, about 12.5 wt%, about
12.6 wt%, about
12.7 wt%, about 12.8 wt%, about 12.9 wt%, about 13.0 wt%, about 13.1 wt%,
about 13.2 wt%,
about 13.3 wt%, about 13.4 wt%, about 13.5 wt%, about 13.6 wt%, about 13.7
wt%, about 13.8
wt%, about 13.9 wt%, about 14.0 wt%, about 14.1 wt%, about 14.2 wt%, about
14.3 wt%, about
14.4 wt%, about 14.5 wt%, about 14.6 wt%, about 14.7 wt%, about 14.8 wt%,
about 14.9 wt%,
about 15.0 wt%, about 15.1 wt%, about 15.2 wt%, about 15.3 wt%, about 15.4
wt%, about 15.5
wt%, about 15.6 wt%, about 15.7 wt%, about 15.8 wt%, about 15.9 wt%, about
16.0 wt%, about
16.1 wt%, about 16.2 wt%, about 16.3 wt%, about 16.4 wt%, about 16.5 wt%,
about 16.6 wt%,
about 16.7 wt%, about 16.8 wt%, about 16.9 wt%, about 17.0 wt%, about 17.1
wt%, about 17.2
wt%, about 17.3 wt%, about 17.4 wt%, about 17.5 wt%, about 17.6 wt%, about
17.7 wt%, about
17.8 wt%, about 17.9 wt%, about 18.0 wt%, about 18.1 wt%, about 18.2 wt%,
about 18.3 wt%,
about 18.4 wt%, about 18.5 wt%, about 18.6 wt%, about 18.7 wt%, about 18.8
wt%, about 18.9
wt%, about 19.0 wt%, about 19.1 wt%, about 19.2 wt%, about 19.3 wt%, about
19.4 wt%, about
19.5 wt%, about 19.6 wt%, about 19.7 wt%, about 19.8 wt%, about 19.9 wt%,
about 20.0 wt%;
or any range encompassed by the foregoing values; or any combination of the
foregoing values.
[0038] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents comprises therapeutically effective amounts of minoxidil, wherein the
finasteride is
present in an amount of about 0.010 wt%, about 0.015 wt%, about 0.020 wt%,
about 0.025 wt%,
about 0.030 wt%, about 0.035 wt%, about 0.040 wt%, about 0.045 wt%, about
0.050 wt%, about
0.055 wt%, about 0.060 wt%, about 0.065 wt%, about 0.070 wt%, about 0.075 wt%,
about 0.080
wt%, about 0.085 wt%, about 0.090 wt%, about 0.095 wt%, about 0.100 wt%, about
0.105 wt%,
about 0.110 wt%, about 0.115 wt%, about 0.120 wt%, about 0.125 wt%, about
0.130 wt%, about
0.135 wt%, about 0.140 wt%, about 0.145 wt%, about 0.150 wt%, about 0.155 wt%,
about 0.160
wt%, about 0.165 wt%, about 0.170 wt%, about 0.175 wt%, about 0.180 wt%, about
0.185 wt%,
about 0.190 wt%, about 0.195 wt%, about 0.200 wt%, about 0.205 wt%, about
0.210 wt%, about
9
Date Recue/Date Received 2023-08-18
0.215 wt%, about 0.220 wt%, about 0.225 wt%, about 0.230 wt%, about 0.235 wt%,
about 0.240
wt%, about 0.245 wt%, about 0.250 wt%, about 0.255 wt%, about 0.260 wt%, about
0.265 wt%,
about 0.270 wt%, about 0.275 wt%, about 0.280 wt%, about 0.285 wt%, about
0.290 wt%, about
0.295 wt%, about 0.300 wt%, about 0.305 wt%, about 0.310 wt%, about 0.315 wt%,
about 0.320
wt%, about 0.325 wt%, about 0.330 wt%, about 0.335 wt%, about 0.340 wt%, about
0.345 wt%,
about 0.350 wt%, about 0.355 wt%, about 0.360 wt%, about 0.365 wt%, about
0.370 wt%, about
0.375 wt%, about 0.380 wt%, about 0.385 vvt%, about 0.390 wt%, about 0.395
wt%, about 0.400
wt%, about 0.405 wt%, about 0.410 wt%, about 0.415 wt%, about 0.420 wt%, about
0.425 wt%,
about 0.430 wt%, about 0.435 wt%, about 0.440 wt%, about 0.445 wt%, about
0.450 wt%, about
0.455 wt%, about 0.460 wt%, about 0.465 wt%, about 0.470 wt%, about 0.475 wt%,
about 0.480
wt%, about 0.485 wt%, about 0.490 wt%, about 0.495 wt%, about 0.500 wt%; or
any range
encompassed by the foregoing values; or any combination of the foregoing
values.
[0039] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents comprises therapeutically effective amounts of minoxidil, wherein the
dutasteride is
present in an amount of about 0.0005 wt%, about 0.0010 wt%, about 0.0015 wt%,
about 0.0020
wt%, about 0.0025 wt%, about 0.0030 wt%, about 0.0035 wt%, about 0.0040 wt%,
about 0.0045
wt%, about 0.0050 wt%, about 0.0055 wt%, about 0.0060 wt%, about 0.0065 wt%,
about 0.0070
wt%, about 0.0075 wt%, about 0.0080 wt%, about 0.0085 wt%, about 0.0090 wt%,
about 0.0095
wt%, about 0.0100 wt%, about 0.0105 wt%, about 0.0110 wt%, about 0.0115 wt%,
about 0.0120
wt%, about 0.0125 wt%, about 0.0130 wt%, about 0.0135 wt%, about 0.0140 wt%,
about 0.0145
wt%, about 0.0150 wt%, about 0.0155 wt%, about 0.0160 wt%, about 0.0165 wt%,
about 0.0170
wt%, about 0.0175 wt%, about 0.0180 wt%, about 0.0185 wt%, about 0.0190 wt%,
about 0.0195
wt%, about 0.0200 wt%, about 0.0205 wt%, about 0.0210 wt%, about 0.0215 wt%,
about 0.0220
wt%, about 0.0225 wt%, about 0.0230 wt%, about 0.0235 wt%, about 0.0240 wt%,
about 0.0245
wt%, about 0.0250 wt%, about 0.0255 wt%, about 0.0260 wt%, about 0.0265 wt%,
about 0.0270
wt%, about 0.0275 wt%, about 0.0280 wt%, about 0.0285 wt%, about 0.0290 wt%,
about 0.0295
wt%, about 0.0300 wt%; or any range encompassed by the foregoing values; or
any
combination of the foregoing values.
[0040] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents, wherein the one or more compounding agents comprise ethoxy diglycol,
propylene
Date Recue/Date Received 2023-08-18
glycol, a gel base for gel-cream emulsions, a cream base, a silicone base, or
combinations
thereof.
[0041] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising
azelaic acid, minoxidil,
finasteride, and dutasteride; and one or more compounding agents, wherein the
formulation
comprises therapeutically effective amounts of azelaic acid, minoxidil,
finasteride, and
dutasteride; and the one or more compounding agents are present as follows:
about 1 vol/wt%
to about 10 vol/wt% ethoxy diglycol; about 1 vol/wt% to about 10 vol/wt%
propylene glycol;
about 5 wt% to about 20 wt% of a gel base for gel-cream emulsions; about 15
wt% to about 35
wt% of a cream base; and about 15 wt% to about 50 wt% of a silicone base;
wherein the wt% of
a component is based on the total weight of the therapeutic composition and
one or more
compounding agents; and wherein the vol/wt% of a component is based on the
total weight of
the therapeutic composition and one or more compounding agents.
[0042] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising
azelaic acid, minoxidil,
finasteride, and dutasteride; and one or more compounding agents wherein the
formulation
comprises therapeutically effective amounts of azelaic acid, minoxidil,
finasteride, and
dutasteride; and the one or more compounding agents are present as follows:
about 4 vol/wt%
to about 6 vol/wt% ethoxy diglycol; about 2.5 vol/wt% to about 4.5 vol/wt%
propylene glycol;
about 8 wt% to about 14 wt% of a gel base for gel-cream emulsions; about 20
wt% to about 30
wt% of a cream base; and about 20 wt% to about 30 wt% of a silicone base;
wherein the wt% of
a component is based on the total weight of the therapeutic composition and
one or more
compounding agents; and wherein the vol/wt% of a component is based on the
total weight of
the therapeutic composition and one or more compounding agents.
[0043] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising
azelaic acid, minoxidil,
finasteride, and dutasteride; and one or more compounding agents; wherein
formulation
comprising: a therapeutic composition comprising therapeutically effective
amounts of azelaic
acid, minoxidil, finasteride, and dutasteride; and wherein the one or more
compounding agents
are present as follows: about 6 vol/wt% ethoxy diglycol; about 3.5 vol/wt%
propylene glycol;
about 11 wt% of a gel base for gel-cream emulsions; about 21 wt% to about 23
wt% of a cream
base; and about 26 wt% to about 29 wt% of a silicone base; wherein the wt% of
a component is
based on the total weight of the therapeutic composition and one or more
compounding agents;
11
Date Recue/Date Received 2023-08-18
and wherein the vol/wt% of a component is based on the total weight of the
therapeutic
composition and one or more compounding agents.
[0044] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents; wherein formulation comprises therapeutically effective amounts of
azelaic acid,
minoxidil, finasteride, and dutasteride; and wherein the formulation comprises
ethoxy glycol in
an amount of about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about
1.4 wt%,
about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%,
about 2.0 wt%,
about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%,
about 2.6 wt%,
about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%,
about 3.2 wt%,
about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%,
about 3.8 wt%,
about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%,
about 4.4 wt%,
about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%,
about 5.0 wt%,
about 5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%,
about 5.6 wt%,
about 5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%,
about 6.2 wt%,
about 6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%,
about 6.8 wt%,
about 6.9 wt%, about 7.0 wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%,
about 7.4 wt%,
about 7.5 wt%, about 7.6 wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%,
about 8.0 wt%,
about 8.1 wt%, about 8.2 wt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%,
about 8.6 wt%,
about 8.7 wt%, about 8.8 wt%, about 8.9 wt%, about 9.0 vvt%, about 9.1 wt%,
about 9.2 wt%,
about 9.3 wt%, about 9.4 wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%,
about 9.8 wt%,
about 9.9 wt%, about 10.0 wt%; or any range encompassed by the foregoing
values; or any
combination of the foregoing values.
[0045] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents; wherein formulation comprises therapeutically effective amounts of
azelaic acid,
minoxidil, finasteride, and dutasteride; and wherein the formulation comprises
propylene glycol
in an amount of about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%,
about 1.4 wt%,
about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%,
about 2.0 wt%,
about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%,
about 2.6 wt%,
about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%,
about 3.2 wt%,
12
Date Recue/Date Received 2023-08-18
about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%,
about 3.8 wt%,
about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%,
about 4.4 wt%,
about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%,
about 5.0 wt%,
about 5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%,
about 5.6 wt%,
about 5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%,
about 6.2 wt%,
about 6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%,
about 6.8 wt%,
about 6.9 wt%, about 7.0 wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%,
about 7.4 wt%,
about 7.5 wt%, about 7.6 wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%,
about 8.0 wt%,
about 8.1 wt%, about 8.2 wt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%,
about 8.6 wt%,
about 8.7 wt%, about 8.8 wt%, about 8.9 wt%, about 9.0 vvt%, about 9.1 wt%,
about 9.2 wt%,
about 9.3 wt%, about 9.4 wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%,
about 9.8 wt%,
about 9.9 wt%, about 10.0 wt%; or any range encompassed by the foregoing
values; or any
combination of the foregoing values.
[0046] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents; wherein formulation comprises therapeutically effective amounts of
azelaic acid,
minoxidil, finasteride, and dutasteride; and wherein the formulation comprises
a gel base for gel-
cream emulsions in an amount of about 5.0 wt%, about 5.1 wt%, about 5.2 wt%,
about 5.3 wt%,
about 5.4 wt%, about 5.5 wt%, about 5.6 wt%, about 5.7 wt%, about 5.8 wt%,
about 5.9 wt%,
about 6.0 wt%, about 6.1 wt%, about 6.2 wt%, about 6.3 vvt%, about 6.4 wt%,
about 6.5 wt%,
about 6.6 wt%, about 6.7 wt%, about 6.8 wt%, about 6.9 wt%, about 7.0 wt%,
about 7.1 wt%,
about 7.2 wt%, about 7.3 wt%, about 7.4 wt%, about 7.5 wt%, about 7.6 wt%,
about 7.7 wt%,
about 7.8 wt%, about 7.9 wt%, about 8.0 wt%, about 8.1 wt%, about 8.2 wt%,
about 8.3 wt%,
about 8.4 wt%, about 8.5 wt%, about 8.6 wt%, about 8.7 wt%, about 8.8 wt%,
about 8.9 wt%,
about 9.0 wt%, about 9.1 wt%, about 9.2 wt%, about 9.3 wt%, about 9.4 wt%,
about 9.5 wt%,
about 9.6 wt%, about 9.7 wt%, about 9.8 wt%, about 9.9 wt%, about 10.0 wt%,
about 10.1 wt%,
about 10.2 wt%, about 10.3 wt%, about 10.4 wt%, about 10.5 wt%, about 10.6
wt%, about 10.7
wt%, about 10.8 wt%, about 10.9 wt%, about 11.0 wt%, about 11.1 wt%, about
11.2 wt%, about
11.3 wt%, about 11.4 wt%, about 11.5 wt%, about 11.6 wt%, about 11.7 wt%,
about 11.8 wt%,
about 11.9 wt%, about 12.0 wt%, about 12.1 wt%, about 12.2 wt%, about 12.3
wt%, about 12.4
wt%, about 12.5 wt%, about 12.6 wt%, about 12.7 wt%, about 12.8 wt%, about
12.9 wt%, about
13.0 wt%, about 13.1 wt%, about 13.2 wt%, about 13.3 wt%, about 13.4 wt%,
about 13.5 wt%,
about 13.6 wt%, about 13.7 wt%, about 13.8 wt%, about 13.9 wt%, about 14.0
wt%, about 14.1
13
Date Recue/Date Received 2023-08-18
wt%, about 14.2 wt%, about 14.3 wt%, about 14.4 wt%, about 14.5 wt%, about
14.6 wt%, about
14.7 wt%, about 14.8 wt%, about 14.9 wt%, about 15.0 wt%, about 15.1 wt%,
about 15.2 wt%,
about 15.3 wt%, about 15.4 wt%, about 15.5 wt%, about 15.6 wt%, about 15.7
wt%, about 15.8
wt%, about 15.9 wt%, about 16.0 wt%, about 16.1 wt%, about 16.2 wt%, about
16.3 wt%, about
16.4 wt%, about 16.5 wt%, about 16.6 wt%, about 16.7 wt%, about 16.8 wt%,
about 16.9 wt%,
about 17.0 wt%, about 17.1 wt%, about 17.2 wt%, about 17.3 wt%, about 17.4
wt%, about 17.5
wt%, about 17.6 wt%, about 17.7 wt%, about 17.8 wt%, about 17.9 wt%, about
18.0 wt%, about
18.1 wt%, about 18.2 wt%, about 18.3 wt%, about 18.4 wt%, about 18.5 wt%,
about 18.6 wt%,
about 18.7 wt%, about 18.8 wt%, about 18.9 wt%, about 19.0 wt%, about 19.1
wt%, about 19.2
wt%, about 19.3 wt%, about 19.4 wt%, about 19.5 wt%, about 19.6 wt%, about
19.7 wt%, about
19.8 wt%, about 19.9 wt%, about 20.0 wt%; or any range encompassed by the
foregoing
values; or any combination of the foregoing values.
[0047] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents; wherein formulation comprises therapeutically effective amounts of
azelaic acid,
minoxidil, finasteride, and dutasteride; and wherein the formulation comprises
a cream base in
an amount of about 15.0 wt%, about 15.1 wt%, about 15.2 wt%, about 15.3 wt%,
about 15.4
wt%, about 15.5 wt%, about 15.6 wt%, about 15.7 wt%, about 15.8 wt%, about
15.9 wt%, about
16.0 wt%, about 16.1 wt%, about 16.2 wt%, about 16.3 wt%, about 16.4 wt%,
about 16.5 wt%,
about 16.6 wt%, about 16.7 wt%, about 16.8 wt%, about 16.9 wt%, about 17.0
wt%, about 17.1
wt%, about 17.2 wt%, about 17.3 wt%, about 17.4 wt%, about 17.5 wt%, about
17.6 wt%, about
17.7 wt%, about 17.8 wt%, about 17.9 wt%, about 18.0 wt%, about 18.1 wt%,
about 18.2 wt%,
about 18.3 wt%, about 18.4 wt%, about 18.5 wt%, about 18.6 wt%, about 18.7
wt%, about 18.8
wt%, about 18.9 wt%, about 19.0 wt%, about 19.1 wt%, about 19.2 wt%, about
19.3 wt%, about
19.4 wt%, about 19.5 wt%, about 19.6 wt%, about 19.7 wt%, about 19.8 wt%,
about 19.9 wt%,
about 20.0 wt%, about 20.1 wt%, about 20.2 wt%, about 20.3 wt%, about 20.4
wt%, about 20.5
wt%, about 20.6 wt%, about 20.7 wt%, about 20.8 wt%, about 20.9 wt%, about
21.0 wt%, about
21.1 wt%, about 21.2 wt%, about 21.3 wt%, about 21.4 wt%, about 21.5 wt%,
about 21.6 wt%,
about 21.7 wt%, about 21.8 wt%, about 21.9 wt%, about 22.0 wt%, about 22.1
wt%, about 22.2
wt%, about 22.3 wt%, about 22.4 wt%, about 22.5 wt%, about 22.6 wt%, about
22.7 wt%, about
22.8 wt%, about 22.9 wt%, about 23.0 wt%, about 23.1 wt%, about 23.2 wt%,
about 23.3 wt%,
about 23.4 wt%, about 23.5 wt%, about 23.6 wt%, about 23.7 wt%, about 23.8
wt%, about 23.9
wt%, about 24.0 wt%, about 24.1 wt%, about 24.2 wt%, about 24.3 wt%, about
24.4 wt%, about
14
Date Recue/Date Received 2023-08-18
24.5 wt%, about 24.6 wt%, about 24.7 wt%, about 24.8 wt%, about 24.9 wt%,
about 25.0 wt%,
about 25.1 wt%, about 25.2 wt%, about 25.3 wt%, about 25.4 wt%, about 25.5
wt%, about 25.6
wt%, about 25.7 wt%, about 25.8 wt%, about 25.9 wt%, about 26.0 wt%, about
26.1 wt%, about
26.2 wt%, about 26.3 wt%, about 26.4 wt%, about 26.5 wt%, about 26.6 wt%,
about 26.7 wt%,
about 26.8 wt%, about 26.9 wt%, about 27.0 wt%, about 27.1 wt%, about 27.2
wt%, about 27.3
wt%, about 27.4 wt%, about 27.5 wt%, about 27.6 wt%, about 27.7 wt%, about
27.8 wt%, about
27.9 wt%, about 28.0 wt%, about 28.1 wt%, about 28.2 wt%, about 28.3 wt%,
about 28.4 wt%,
about 28.5 wt%, about 28.6 wt%, about 28.7 wt%, about 28.8 wt%, about 28.9
wt%, about 29.0
wt%, about 29.1 wt%, about 29.2 wt%, about 29.3 wt%, about 29.4 wt%, about
29.5 wt%, about
29.6 wt%, about 29.7 wt%, about 29.8 wt%, about 29.9 wt%, about 30.0 wt%,
about 30.1 wt%,
about 30.2 wt%, about 30.3 wt%, about 30.4 wt%, about 30.5 wt%, about 30.6
wt%, about 30.7
wt%, about 30.8 wt%, about 30.9 wt%, about 31.0 wt%, about 31.1 wt%, about
31.2 wt%, about
31.3 wt%, about 31.4 wt%, about 31.5 wt%, about 31.6 wt%, about 31.7 wt%,
about 31.8 wt%,
about 31.9 wt%, about 32.0 wt%, about 32.1 wt%, about 32.2 wt%, about 32.3
wt%, about 32.4
wt%, about 32.5 wt%, about 32.6 wt%, about 32.7 wt%, about 32.8 wt%, about
32.9 wt%, about
33.0 wt%, about 33.1 wt%, about 33.2 wt%, about 33.3 wt%, about 33.4 wt%,
about 33.5 wt%,
about 33.6 wt%, about 33.7 wt%, about 33.8 wt%, about 33.9 wt%, about 34.0
wt%, about 34.1
wt%, about 34.2 wt%, about 34.3 wt%, about 34.4 wt%, about 34.5 wt%, about
34.6 wt%, about
34.7 wt%, about 34.8 wt%, about 34.9 wt%, about 35.0 wt%; or any range
encompassed by the
foregoing values; or any combination of the foregoing values.
[0048] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising azelaic acid, minoxidil, finasteride, and dutasteride; and one or
more compounding
agents; wherein formulation comprises therapeutically effective amounts of
azelaic acid,
minoxidil, finasteride, and dutasteride; and wherein the formulation comprises
a silicone base in
an amount of about 15.0 wt%, about 15.1 wt%, about 15.2 wt%, about 15.3 wt%,
about 15.4
wt%, about 15.5 wt%, about 15.6 wt%, about 15.7 wt%, about 15.8 wt%, about
15.9 wt%, about
16.0 wt%, about 16.1 wt%, about 16.2 wt%, about 16.3 wt%, about 16.4 wt%,
about 16.5 wt%,
about 16.6 wt%, about 16.7 wt%, about 16.8 wt%, about 16.9 wt%, about 17.0
wt%, about 17.1
wt%, about 17.2 wt%, about 17.3 wt%, about 17.4 wt%, about 17.5 wt%, about
17.6 wt%, about
17.7 wt%, about 17.8 wt%, about 17.9 wt%, about 18.0 wt%, about 18.1 wt%,
about 18.2 wt%,
about 18.3 wt%, about 18.4 wt%, about 18.5 wt%, about 18.6 wt%, about 18.7
wt%, about 18.8
wt%, about 18.9 wt%, about 19.0 wt%, about 19.1 wt%, about 19.2 wt%, about
19.3 wt%, about
19.4 wt%, about 19.5 wt%, about 19.6 wt%, about 19.7 wt%, about 19.8 wt%,
about 19.9 wt%,
Date Recue/Date Received 2023-08-18
about 20.0 wt%, about 20.1 wt%, about 20.2 wt%, about 20.3 wt%, about 20.4
wt%, about 20.5
wt%, about 20.6 wt%, about 20.7 wt%, about 20.8 wt%, about 20.9 wt%, about
21.0 wt%, about
21.1 wt%, about 21.2 wt%, about 21.3 wt%, about 21.4 wt%, about 21.5 wt%,
about 21.6 wt%,
about 21.7 wt%, about 21.8 wt%, about 21.9 wt%, about 22.0 wt%, about 22.1
wt%, about 22.2
wt%, about 22.3 wt%, about 22.4 wt%, about 22.5 wt%, about 22.6 wt%, about
22.7 wt%, about
22.8 wt%, about 22.9 wt%, about 23.0 wt%, about 23.1 wt%, about 23.2 wt%,
about 23.3 wt%,
about 23.4 wt%, about 23.5 wt%, about 23.6 wt%, about 23.7 wt%, about 23.8
wt%, about 23.9
wt%, about 24.0 wt%, about 24.1 wt%, about 24.2 wt%, about 24.3 wt%, about
24.4 wt%, about
24.5 wt%, about 24.6 wt%, about 24.7 wt%, about 24.8 wt%, about 24.9 wt%,
about 25.0 wt%,
about 25.1 wt%, about 25.2 wt%, about 25.3 wt%, about 25.4 wt%, about 25.5
wt%, about 25.6
wt%, about 25.7 wt%, about 25.8 wt%, about 25.9 wt%, about 26.0 wt%, about
26.1 wt%, about
26.2 wt%, about 26.3 wt%, about 26.4 wt%, about 26.5 wt%, about 26.6 wt%,
about 26.7 wt%,
about 26.8 wt%, about 26.9 wt%, about 27.0 wt%, about 27.1 wt%, about 27.2
wt%, about 27.3
wt%, about 27.4 wt%, about 27.5 wt%, about 27.6 wt%, about 27.7 wt%, about
27.8 wt%, about
27.9 wt%, about 28.0 wt%, about 28.1 wt%, about 28.2 wt%, about 28.3 wt%,
about 28.4 wt%,
about 28.5 wt%, about 28.6 wt%, about 28.7 wt%, about 28.8 wt%, about 28.9
wt%, about 29.0
wt%, about 29.1 wt%, about 29.2 wt%, about 29.3 wt%, about 29.4 wt%, about
29.5 wt%, about
29.6 wt%, about 29.7 wt%, about 29.8 wt%, about 29.9 wt%, about 30.0 wt%,
about 30.1 wt%,
about 30.2 wt%, about 30.3 wt%, about 30.4 wt%, about 30.5 wt%, about 30.6
wt%, about 30.7
wt%, about 30.8 wt%, about 30.9 wt%, about 31.0 wt%, about 31.1 wt%, about
31.2 wt%, about
31.3 wt%, about 31.4 wt%, about 31.5 wt%, about 31.6 wt%, about 31.7 wt%,
about 31.8 wt%,
about 31.9 wt%, about 32.0 wt%, about 32.1 wt%, about 32.2 wt%, about 32.3
wt%, about 32.4
wt%, about 32.5 wt%, about 32.6 wt%, about 32.7 wt%, about 32.8 wt%, about
32.9 wt%, about
33.0 wt%, about 33.1 wt%, about 33.2 wt%, about 33.3 wt%, about 33.4 wt%,
about 33.5 wt%,
about 33.6 wt%, about 33.7 wt%, about 33.8 wt%, about 33.9 wt%, about 34.0
wt%, about 34.1
wt%, about 34.2 wt%, about 34.3 wt%, about 34.4 wt%, about 34.5 wt%, about
34.6 wt%, about
34.7 wt%, about 34.8 wt%, about 34.9 wt%, about 35.0 wt%, about 35.1 wt%,
about 35.2 wt%,
about 35.3 wt%, about 35.4 wt%, about 35.5 wt%, about 35.6 wt%, about 35.7
wt%, about 35.8
wt%, about 35.9 wt%, about 36.0 wt%, about 36.1 wt%, about 36.2 wt%, about
36.3 wt%, about
36.4 wt%, about 36.5 wt%, about 36.6 wt%, about 36.7 wt%, about 36.8 wt%,
about 36.9 wt%,
about 37.0 wt%, about 37.1 wt%, about 37.2 wt%, about 37.3 wt%, about 37.4
wt%, about 37.5
wt%, about 37.6 wt%, about 37.7 wt%, about 37.8 wt%, about 37.9 wt%, about
38.0 wt%, about
38.1 wt%, about 38.2 wt%, about 38.3 wt%, about 38.4 wt%, about 38.5 wt%,
about 38.6 wt%,
about 38.7 wt%, about 38.8 wt%, about 38.9 wt%, about 39.0 wt%, about 39.1
wt%, about 39.2
16
Date Recue/Date Received 2023-08-18
wt%, about 39.3 wt%, about 39.4 wt%, about 39.5 wt%, about 39.6 wt%, about
39.7 wt%, about
39.8 wt%, about 39.9 wt%, about 40.0 wt%, about 40.1 wt%, about 40.2 wt%,
about 40.3 wt%,
about 40.4 wt%, about 40.5 wt%, about 40.6 wt%, about 40.7 wt%, about 40.8
wt%, about 40.9
wt%, about 41.0 wt%, about 41.1 wt%, about 41.2 wt%, about 41.3 wt%, about
41.4 wt%, about
41.5 wt%, about 41.6 wt%, about 41.7 wt%, about 41.8 wt%, about 41.9 wt%,
about 42.0 wt%,
about 42.1 wt%, about 42.2 wt%, about 42.3 wt%, about 42.4 wt%, about 42.5
wt%, about 42.6
wt%, about 42.7 wt%, about 42.8 wt%, about 42.9 wt%, about 43.0 wt%, about
43.1 wt%, about
43.2 wt%, about 43.3 wt%, about 43.4 wt%, about 43.5 wt%, about 43.6 wt%,
about 43.7 wt%,
about 43.8 wt%, about 43.9 wt%, about 44.0 wt%, about 44.1 wt%, about 44.2
wt%, about 44.3
wt%, about 44.4 wt%, about 44.5 wt%, about 44.6 wt%, about 44.7 wt%, about
44.8 wt%, about
44.9 wt%, about 45.0 wt%, about 45.1 wt%, about 45.2 wt%, about 45.3 wt%,
about 45.4 wt%,
about 45.5 wt%, about 45.6 wt%, about 45.7 wt%, about 45.8 wt%, about 45.9
wt%, about 46.0
wt%, about 46.1 wt%, about 46.2 wt%, about 46.3 wt%, about 46.4 wt%, about
46.5 wt%, about
46.6 wt%, about 46.7 wt%, about 46.8 wt%, about 46.9 wt%, about 47.0 wt%,
about 47.1 wt%,
about 47.2 wt%, about 47.3 wt%, about 47.4 wt%, about 47.5 wt%, about 47.6
wt%, about 47.7
wt%, about 47.8 wt%, about 47.9 wt%, about 48.0 wt%, about 48.1 wt%, about
48.2 wt%, about
48.3 wt%, about 48.4 wt%, about 48.5 wt%, about 48.6 wt%, about 48.7 wt%,
about 48.8 wt%,
about 48.9 wt%, about 49.0 wt%, about 49.1 wt%, about 49.2 wt%, about 49.3
wt%, about 49.4
wt%, about 49.5 wt%, about 49.6 wt%, about 49.7 wt%, about 49.8 wt%, about
49.9 wt%, about
50.0 wt%; or any range encompassed by the foregoing values; or any combination
of the
foregoing values.
[0049] In various aspects, the ethoxy diglycol used in the disclosed
formulations has a specific
gravity of about 0.9 to about 1.10. In a further aspect, the ethoxy diglycol
used in the disclosed
formulations has a specific gravity of about 1.02 to about 1.07. Without
wishing to be bound by a
particular theory, it is believed that the ethoxy diglycol can act as a
carrier for the various
ingredients, including active ingredients, and/or as a skin penetrant.
[0050] In various aspects, the propylene glycol used in the disclosed
formulations has a specific
gravity of about 0.9 to about 1.3. In a further aspect, the propylene glycol
used in the disclosed
formulations has a specific gravity of about 1.05 to about 1.15. Without
wishing to be bound by a
particular theory, it is believed that the propylene glycol can as a viscosity
control agent. That is,
the amount of propylene glycol used can be adjust to achieve a desired
viscosity in the
disclosed formulation.
17
Date Recue/Date Received 2023-08-18
[0051] In a further aspect, the gel base for gel-cream emulsions used in the
disclosed
formulations comprises water and one or more of the following: ammonium
acryloyldimethyltaurate copolymer, aloe barbadensis leaf juice powder,
allatoin, disodium
EDTA, methylchloroisothiazolinone, or methylisothiazolinone. In a still
further aspect, the gel
base for gel-cream emulsions used in the disclosed formulations comprises
water and one or
more of the following: a high molecular weight silicone elastomer gel,
including, but not limited
to, PEG-12 dimethicone/PPG-20 crosspolymer; Butyrospermum park!! (shea
butter); a cross-
tinkled siloxane, including, but not limited to, polysilicone-11; tocopheryl
acetate; or BHT. In a
yet further aspect, the gel base for gel-cream emulsions used in the disclosed
formulations
comprises water and one or more of the following: ammonium
acryloyldimethyltaurate
copolymer, aloe barbadensis leaf juice powder, allatoin, disodium EDTA,
methylchloroisothiazolinone, methylisothiazolinone; a dimethicone, including,
but not limited to
caprylyl methicone; a high molecular weight silicone elastomer gel, including,
but not limited to,
PEG-12 dimethicone/PPG-20 crosspolymer; Butyrospermum park!! (shea butter); a
cross-linkied
siloxane, including, but not limited to, polysilicone-11; tocopheryl acetate;
or BHT.
[0052] In various aspects, the silicone base used in the disclosed
formulations comprise one or
more of the following: cyclopentasiloxane, polysilicone-11, C30-45 alkyl
cetearyl dimethicone
crosspolymer, dimethiconol, phenyl trimethicone, or PEG PPG dimethicone. In a
further aspect,
the silicone base used in the disclosed formulations comprise one or more of
the following:
cyclopetasiloxane, polysilicone-11, laureth-4, macademia seed oil, glycereth-8
esters, phenyl
trimethicone, C30-45 alkyl ceteryl dimethicone crossploymer, dimethiconol, PEG
PPG
dimethicone, PEG-30 dipolyhydroxysterate, Carapa guainesis seed oil, or
Pracaxi Oil, e.g., an
oil derived from the seeds of the Pentaclethra macroloba tree. In a still
further aspect, the
silicone base used in the disclosed formulations comprise one or more of the
following:
cyclopentasiloxane, polysilicone-11, C30-45 alkyl cetearyl dimethicone
crosspolymer,
dimethiconol, phenyl trimethicone, PEG PPG dimethicone, cyclopetasiloxane,
polysilicone-11,
laureth-4, macademia seed oil, glycereth-8 esters, phenyl trimethicone, C30-45
alkyl ceteryl
dimethicone crossploymer, dimethiconol, PEG PPG dimethicone, PEG-30
dipolyhydroxysterate,
Carapa guainesis seed oil, or Pracaxi Oil, e.g., an oil derived from the seeds
of the Pentaclethra
macroloba tree.
[0053] In a further aspect, the silicone base used in the disclosed
formulations further
comprises a one or more fatty acids. In a still further aspect, In various
aspects, the silicone
18
Date Recue/Date Received 2023-08-18
base used in the disclosed formulations further comprises an Carapa
guaianensis seed oil,
macadamia nut oil, laureth-4, PEG 30 dipolyhydroxystearate, or combinations
thereof.
[0054] In various aspects, the silicone base used in the disclosed
formulations has a pH of
about 5.5 to about 6.5. In a further aspect, the silicone base used in the
disclosed formulations
has a pH of about 5.9 to about 6.1.
[0055] In various aspects, the silicone base used in the disclosed
formulations has a specific
gravity of about 0.90 to about 1.30. In a further aspect, the silicon base
used in the disclosed
formulations has a specific gravity of about 1.07 to about 1.20.
[0056] In various aspects, the cream base used in the disclosed formulations
comprise one or
more of the following: purified water, white petrolatum, cetyl alcohol, steryl
alcohol, propylene
glycol, glyerin, sodium lauryl sulfate, diazolidinyl urea, iodopropynyl
butylcarbamate, laureth-23,
glycine soja oil (e.g., a soybean oil derived from the Glycine sofa plant),
one or more fatty acids,
e.g., oleic acid, paraffinum liquidium, lanolin, laneth-16, triethanolamine,
tocopheral acetate,
retinyl palmitate, or Aloe barbadenis leaf powder.
[0057] In various aspects, the disclosed formulations can further comprise
caffeine, saw
palmetto extract, or a combination thereof. Without wishing to be bound by a
particular theory, it
is believed that caffeine can have a beneficial effect in the disclosed
formulation, e.g.,
increasing blood flow in the area to which the disclosed formulation is
applied. Similarly, without
wishing to be bound by a particular theory, it is believed that saw palmetto
extract can have a
beneficial effect in the disclosed formulation, e.g., increasing blood flow in
the area to which the
disclosed formulation is applied.
[0058] In a further aspect, the disclosed formulations can further comprise
caffeine present in
an amount from about 0.0001 wt% to about 0.007 wt%. In a further aspect, the
disclosed
formulations can further comprise caffeine present in an amount of about
0.00010 wt%, about
0.00015 wt%, about 0.00020 wt%, about 0.0025 wt%, about 0.00030 wt%, about
0.00035 wt%,
about 0.00040 wt%, about 0.00045 wt%, about 0.00050 wt%, about 0.00055 wt%,
about
0.00060 wt%, about 0.00065 wt%, about 0.00070 wt%, about 0.00075 wt%, about
0.00080 wt%,
about 0.00085 wt%, about 0.00090 wt%, about 0.00095 wt%, about 0.00100 wt%,
about
0.00105 wt%, about 0.00110 wt%, about 0.00115 wt%, about 0.00120 wt%, about
0.00125 wt%,
about 0.00130 wt%, about 0.00135 wt%, about 0.00140 wt%, about 0.00145 wt%,
about
0.00150 wt%, about 0.00155 wt%, about 0.00160 wt%, about 0.00165 wt%, about
0.00170 wt%,
about 0.00175 wt%, about 0.00180 wt%, about 0.00185 wt%, about 0.00190 wt%,
about
19
Date Recue/Date Received 2023-08-18
0.00195 wt%,about 0.0020 wt%, about 0.0025 wt%, about 0.0030 wt%, about 0.0035
wt%,
about 0.0040 wt%, about 0.0045 wt%, about 0.0050 wt%, about 0.0055 wt%, about
0.0060 wt%,
about 0.0065 wt%, about 0.0070 wt%; or any range encompassed by the foregoing
values; or
any combination of the foregoing values.
[0059] In a further aspect, the disclosed formulations can further comprise
saw palmetto extract
present in an amount from about 0. 1 wt% to about 15 wt%. In a further aspect,
the disclosed
formulations can further comprise saw palmetto extract present in an amount of
about 0.10 wt%,
about 0.20 wt%, about 0.30 wt%, about 0.40 wt%, about 0.50 wt%, about 0.60
wt%, about 0.70
wt%, about 0.80 wt%, about 0.90 wt%, about 1.0 wt%, about 1.1 wt%, about 1.2
wt%, about 1.3
wt%, about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8
wt%, about 1.9
wt%, about 2.0 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4
wt%, about 2.5
wt%, about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0
wt%, about 3.1
wt%, about 3.2 wt%, about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6
wt%, about 3.7
wt%, about 3.8 wt%, about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2
wt%, about 4.3
wt%, about 4.4 wt%, about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8
wt%, about 4.9
wt%, about 5.0 wt%, about 5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4
wt%, about 5.5
wt%, about 5.6 wt%, about 5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0
wt%, about 6.1
wt%, about 6.2 wt%, about 6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6
wt%, about 6.7
wt%, about 6.8 wt%, about 6.9 wt%, about 7.0 wt%, about 7.1 wt%, about 7.2
wt%, about 7.3
wt%, about 7.4 wt%, about 7.5 wt%, about 7.6 wt%, about 7.7 wt%, about 7.8
wt%, about 7.9
wt%, about 8.0 wt%, about 8.1 wt%, about 8.2 wt%, about 8.3 vvt%, about 8.4
wt%, about 8.5
wt%, about 8.6 wt%, about 8.7 wt%, about 8.8 wt%, about 8.9 wt%, about 9.0
wt%, about 9.1
wt%, about 9.2 wt%, about 9.3 wt%, about 9.4 wt%, about 9.5 wt%, about 9.6
wt%, about 9.7
wt%, about 9.8 wt%, about 9.9 wt%, about 10.0 wt%, about 10.1 wt%, about 10.2
wt%, about
10.3 wt%, about 10.4 wt%, about 10.5 wt%, about 10.6 wt%, about 10.7 wt%,
about 10.8 wt%,
about 10.9 wt%, about 11.0 wt%, about 11.1 wt%, about 11.2 wt%, about 11.3
wt%, about 11.4
wt%, about 11.5 wt%, about 11.6 wt%, about 11.7 wt%, about 11.8 wt%, about
11.9 wt%, about
12.0 wt%, about 12.1 wt%, about 12.2 wt%, about 12.3 wt%, about 12.4 wt%,
about 12.5 wt%,
about 12.6 wt%, about 12.7 wt%, about 12.8 wt%, about 12.9 wt%, about 13.0
wt%, about 13.1
wt%, about 13.2 wt%, about 13.3 wt%, about 13.4 wt%, about 13.5 wt%, about
13.6 wt%, about
13.7 wt%, about 13.8 wt%, about 13.9 wt%, about 14.0 wt%, about 14.1 wt%,
about 14.2 wt%,
about 14.3 wt%, about 14.4 wt%, about 14.5 wt%, about 14.6 wt%, about 14.7
wt%, about 14.8
wt%, about 14.9 wt%, about 15.0 wt%; or any range encompassed by the foregoing
values; or
any combination of the foregoing values.
Date Recue/Date Received 2023-08-18
[0060] In a further aspect, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising therapeutically effective amounts of azelaic acid,
minoxidil, finasteride,
and dutasteride; one or more compounding agents; and optionally caffeine
and/or saw palmetto
extract.
[0061] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; one or more
compounding
agents; and optionally caffeine and/or saw palmetto extract; wherein the
formulation comprises
therapeutically effective amounts of azelaic acid, minoxidil, finasteride, and
dutasteride as
follows: about 0.100 wt% to about 0.500 wt% azelaic acid; about 10 wt% to
about 20 wt%
minoxidil; about 0.05 wt% to about 0.50 wt% finasteride; and about 0.001 wt%
to about 0.030
wt% dutasteride; wherein the wt% of a component is based on the total weight
of the
therapeutic composition; and one or more compound agents.
[0062] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; one or more
compounding
agents; and optionally caffeine and/or saw palmetto extract; wherein the
formulation comprises
therapeutically effective amounts of azelaic acid, minoxidil, finasteride, and
dutasteride as
follows: about 0.300 wt% to about 0.400 wt% azelaic acid; about 12 wt% to
about 17 wt%
minoxidil; about 0.10 wt% to about 0.30 wt% finasteride; and about 0.005 wt%
to about 0.015
vvt% dutasteride; wherein the wt% of a component is based on the total weight
of the
therapeutic composition; and one or more compounding agents.
[0063] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; one or more
compounding
agents; and optionally caffeine and/or saw palmetto extract; wherein the
formulation comprises
therapeutically effective amounts of azelaic acid, minoxidil, finasteride, and
dutasteride as
follows: about 0.325 wt% azelaic acid; about 15 wt% minoxidil; about 0.20 wt%
finasteride; and
about 0.010 wt% dutasteride; wherein the wt% of a component is based on the
total weight of
the therapeutic composition and one or more compounding agents.
[0064] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; one or more
compounding
agents; and optionally caffeine and/or saw palmetto extract; wherein the
azelaic acid is present
in an amount of about 0.100 wt%, about 0.105 wt%, about 0.110 wt%, about 0.115
wt%, about
0.120 wt%, about 0.125 wt%, about 0.130 wt%, about 0.135 wt%, about 0.140 wt%,
about 0.145
21
Date Recue/Date Received 2023-08-18
wt%, about 0.150 wt%, about 0.155 wt%, about 0.160 wt%, about 0.165 wt%, about
0.170 wt%,
about 0.175 wt%, about 0.180 wt%, about 0.185 wt%, about 0.190 wt%, about
0.195 wt%, about
0.200 wt%, about 0.205 wt%, about 0.210 wt%, about 0.215 wt%, about 0.220 wt%,
about 0.225
wt%, about 0.230 wt%, about 0.235 wt%, about 0.240 wt%, about 0.245 wt%, about
0.250 wt%,
about 0.255 wt%, about 0.260 wt%, about 0.265 wt%, about 0.270 wt%, about
0.275 wt%, about
0.280 wt%, about 0.285 wt%, about 0.290 wt%, about 0.295 wt%, about 0.300 wt%,
about 0.305
wt%, about 0.310 wt%, about 0.315 wt%, about 0.320 wt%, about 0.325 wt%, about
0.330 wt%,
about 0.335 wt%, about 0.340 wt%, about 0.345 wt%, about 0.350 wt%, about
0.355 wt%, about
0.360 wt%, about 0.365 wt%, about 0.370 wt%, about 0.375 wt%, about 0.380 wt%,
about 0.385
wt%, about 0.390 wt%, about 0.395 wt%, about 0.400 wt%, about 0.405 wt%, about
0.410 wt%,
about 0.415 wt%, about 0.420 wt%, about 0.425 wt%, about 0.430 wt%, about
0.435 wt%, about
0.440 wt%, about 0.445 wt%, about 0.450 wt%, about 0.455 wt%, about 0.460 wt%,
about 0.465
wt%, about 0.470 wt%, about 0.475 wt%, about 0.480 wt%, about 0.485 wt%, about
0.490 wt%,
about 0.495 wt%, about 0.500 wt%; or any range encompassed by the foregoing
values; or any
combination of the foregoing values.
[0065] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; one or more
compounding
agents; and optionally caffeine and/or saw palmetto extract; wherein the
minoxidil is present in
an amount of about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about
1.4 wt%,
about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%,
about 2.0 wt%,
about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 vvt%, about 2.5 wt%,
about 2.6 wt%,
about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%,
about 3.2 wt%,
about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%,
about 3.8 wt%,
about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%,
about 4.4 wt%,
about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%,
about 5.0 wt%,
about 5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%,
about 5.6 wt%,
about 5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%,
about 6.2 wt%,
about 6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%,
about 6.8 wt%,
about 6.9 wt%, about 7.0 wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%,
about 7.4 wt%,
about 7.5 wt%, about 7.6 wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%,
about 8.0 wt%,
about 8.1 wt%, about 8.2 wt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%,
about 8.6 wt%,
about 8.7 wt%, about 8.8 wt%, about 8.9 wt%, about 9.0 wt%, about 9.1 wt%,
about 9.2 wt%,
about 9.3 wt%, about 9.4 wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%,
about 9.8 wt%,
about 9.9 wt%, about 10.0 wt%, about 10.1 wt%, about 10.2 wt%, about 10.3 wt%,
about 10.4
22
Date Recue/Date Received 2023-08-18
wt%, about 10.5 wt%, about 10.6 wt%, about 10.7 wt%, about 10.8 wt%, about
10.9 wt%, about
11.0 wt%, about 11.1 wt%, about 11.2 wt%, about 11.3 wt%, about 11.4 wt%,
about 11.5 wt%,
about 11.6 wt%, about 11.7 wt%, about 11.8 wt%, about 11.9 wt%, about 12.0
wt%, about 12.1
wt%, about 12.2 wt%, about 12.3 wt%, about 12.4 wt%, about 12.5 wt%, about
12.6 wt%, about
12.7 wt%, about 12.8 wt%, about 12.9 wt%, about 13.0 wt%, about 13.1 wt%,
about 13.2 wt%,
about 13.3 wt%, about 13.4 wt%, about 13.5 wt%, about 13.6 wt%, about 13.7
wt%, about 13.8
wt%, about 13.9 wt%, about 14.0 wt%, about 14.1 wt%, about 14.2 wt%, about
14.3 wt%, about
14.4 wt%, about 14.5 wt%, about 14.6 wt%, about 14.7 wt%, about 14.8 wt%,
about 14.9 wt%,
about 15.0 wt%, about 15.1 wt%, about 15.2 wt%, about 15.3 wt%, about 15.4
wt%, about 15.5
wt%, about 15.6 wt%, about 15.7 wt%, about 15.8 wt%, about 15.9 wt%, about
16.0 wt%, about
16.1 wt%, about 16.2 wt%, about 16.3 wt%, about 16.4 wt%, about 16.5 wt%,
about 16.6 wt%,
about 16.7 wt%, about 16.8 wt%, about 16.9 wt%, about 17.0 wt%, about 17.1
wt%, about 17.2
wt%, about 17.3 wt%, about 17.4 wt%, about 17.5 wt%, about 17.6 wt%, about
17.7 wt%, about
17.8 wt%, about 17.9 wt%, about 18.0 wt%, about 18.1 wt%, about 18.2 wt%,
about 18.3 wt%,
about 18.4 wt%, about 18.5 wt%, about 18.6 wt%, about 18.7 wt%, about 18.8
wt%, about 18.9
wt%, about 19.0 wt%, about 19.1 wt%, about 19.2 wt%, about 19.3 wt%, about
19.4 wt%, about
19.5 wt%, about 19.6 wt%, about 19.7 wt%, about 19.8 wt%, about 19.9 wt%,
about 20.0 wt%;
or any range encompassed by the foregoing values; or any combination of the
foregoing values.
[0066] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; one or more
compounding
agents; and optionally caffeine and/or saw palmetto extract; wherein the
finasteride is present in
an amount of about 0.010 wt%, about 0.015 wt%, about 0.020 wt%, about 0.025
wt%, about
0.030 wt%, about 0.035 wt%, about 0.040 wt%, about 0.045 wt%, about 0.050 wt%,
about 0.055
wt%, about 0.060 wt%, about 0.065 wt%, about 0.070 wt%, about 0.075 wt%, about
0.080 wt%,
about 0.085 wt%, about 0.090 wt%, about 0.095 wt%, about 0.100 wt%, about
0.105 wt%, about
0.110 wt%, about 0.115 wt%, about 0.120 wt%, about 0.125 wt%, about 0.130 wt%,
about 0.135
wt%, about 0.140 wt%, about 0.145 wt%, about 0.150 wt%, about 0.155 wt%, about
0.160 wt%,
about 0.165 wt%, about 0.170 wt%, about 0.175 wt%, about 0.180 wt%, about
0.185 wt%, about
0.190 wt%, about 0.195 wt%, about 0.200 wt%, about 0.205 wt%, about 0.210 wt%,
about 0.215
wt%, about 0.220 wt%, about 0.225 wt%, about 0.230 wt%, about 0.235 wt%, about
0.240 wt%,
about 0.245 wt%, about 0.250 wt%, about 0.255 wt%, about 0.260 wt%, about
0.265 wt%, about
0.270 wt%, about 0.275 wt%, about 0.280 wt%, about 0.285 wt%, about 0.290 wt%,
about 0.295
wt%, about 0.300 wt%, about 0.305 wt%, about 0.310 wt%, about 0.315 wt%, about
0.320 wt%,
about 0.325 wt%, about 0.330 wt%, about 0.335 wt%, about 0.340 wt%, about
0.345 wt%, about
23
Date Recue/Date Received 2023-08-18
0.350 wt%, about 0.355 wt%, about 0.360 wt%, about 0.365 wt%, about 0.370 wt%,
about 0.375
wt%, about 0.380 wt%, about 0.385 wt%, about 0.390 wt%, about 0.395 wt%, about
0.400 wt%,
about 0.405 wt%, about 0.410 wt%, about 0.415 wt%, about 0.420 wt%, about
0.425 wt%, about
0.430 wt%, about 0.435 wt%, about 0.440 wt%, about 0.445 wt%, about 0.450 wt%,
about 0.455
wt%, about 0.460 wt%, about 0.465 wt%, about 0.470 wt%, about 0.475 wt%, about
0.480 wt%,
about 0.485 wt%, about 0.490 wt%, about 0.495 wt%, about 0.500 wt%; or any
range
encompassed by the foregoing values; or any combination of the foregoing
values.
[0067] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid, minoxidil, finasteride, and dutasteride; one or more
compounding
agents; and optionally caffeine and/or saw palmetto extract; wherein the
dutasteride is present
in an amount of about 0.0005 wt%, about 0.0010 wt%, about 0.0015 wt%, about
0.0020 wt%,
about 0.0025 wt%, about 0.0030 wt%, about 0.0035 wt%, about 0.0040 wt%, about
0.0045 wt%,
about 0.0050 wt%, about 0.0055 wt%, about 0.0060 wt%, about 0.0065 wt%, about
0.0070 wt%,
about 0.0075 wt%, about 0.0080 wt%, about 0.0085 wt%, about 0.0090 wt%, about
0.0095 wt%,
about 0.0100 wt%, about 0.0105 wt%, about 0.0110 wt%, about 0.0115 wt%, about
0.0120 wt%,
about 0.0125 wt%, about 0.0130 wt%, about 0.0135 wt%, about 0.0140 wt%, about
0.0145 wt%,
about 0.0150 wt%, about 0.0155 wt%, about 0.0160 wt%, about 0.0165 wt%, about
0.0170 wt%,
about 0.0175 wt%, about 0.0180 wt%, about 0.0185 wt%, about 0.0190 wt%, about
0.0195 wt%,
about 0.0200 wt%, about 0.0205 wt%, about 0.0210 wt%, about 0.0215 wt%, about
0.0220 wt%,
about 0.0225 wt%, about 0.0230 wt%, about 0.0235 wt%, about 0.0240 wt%, about
0.0245 wt%,
about 0.0250 wt%, about 0.0255 wt%, about 0.0260 wt%, about 0.0265 wt%, about
0.0270 wt%,
about 0.0275 wt%, about 0.0280 wt%, about 0.0285 wt%, about 0.0290 wt%, about
0.0295 wt%,
about 0.0300 wt%; or any range encompassed by the foregoing values; or any
combination of
the foregoing values.
[0068] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising therapeutically effective amounts of azelaic acid,
minoxidil, finasteride,
and dutasteride; one or more compounding agents; and optionally caffeine
and/or saw palmetto
extract; wherein the one or more compounding agents comprise ethoxy diglycol,
propylene
glycol, a gel base for gel-cream emulsions, a cream base, a silicone base, or
combinations
thereof.
[0069] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
24
Date Recue/Date Received 2023-08-18
composition comprising therapeutically effective amounts of azelaic acid,
minoxidil, finasteride,
dutasteride; one or more compounding agents; and optionally caffeine and/or
saw palmetto
extract; wherein formulation comprises a therapeutically effective amount of
azelaic acid,
minoxidil, finasteride, and dutasteride; and the one or more compounding
agents are present as
follows: about 1 vol/wt% to about 10 vol/wt% ethoxy diglycol; about 1 vol/wt%
to about 10
vol/wt% propylene glycol; about 5 wt% to about 20 wt% of a gel base for gel-
cream emulsions;
about 15 wt% to about 35 wt% of a cream base; and about 15 wt% to about 50 wt%
of a silicone
base; wherein the wt% of a component is based on the total weight of the
therapeutic
composition and one or more compounding agents; and wherein the vol/wt% of a
component is
based on the total weight of the therapeutic composition and one or more
compounding agents.
[0070] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising therapeutically effective amounts of azelaic acid,
minoxidil, finasteride,
and dutasteride; one or more compounding agents; and optionally caffeine
and/or saw palmetto
extract; wherein formulation comprises a therapeutically effective amount of
azelaic acid,
minoxidil, finasteride, and dutasteride; and the one or more compounding
agents are present as
follows: about 4 vol/wt% to about 6 vol/wt% ethoxy diglycol; about 2.5 vol/wt%
to about 4.5
vol/wt% propylene glycol; about 8 wt% to about 14 wt% of a gel base for gel-
cream emulsions;
about 20 wt% to about 30 wt% of a cream base; and about 20 wt% to about 30 wt%
of a silicone
base; wherein the wt% of a component is based on the total weight of the
therapeutic
composition and one or more compounding agents; and wherein the vol/wt% of a
component is
based on the total weight of the therapeutic composition and one or more
compounding agents.
[0071] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising therapeutically effective amounts of azelaic acid,
minoxidil, finasteride,
and dutasteride; one or more compounding agents; and optionally caffeine
and/or saw palmetto
extract; wherein formulation comprises a therapeutically effective amount of
azelaic acid,
minoxidil, finasteride, and dutasteride; and the one or more compounding
agents are present as
follows: about 6 vol/wt% ethoxy diglycol; about 3.5 vol/wt% propylene glycol;
about 11 wt% of a
gel base for gel-cream emulsions; about 21 wt% to about 23 wt% of a cream
base; and about
26 wt% to about 29 wt% of a silicone base; wherein the wt% of a component is
based on the
total weight of the therapeutic composition and one or more compounding
agents; and wherein
Date Recue/Date Received 2023-08-18
the vol/wt% of a component is based on the total weight of the therapeutic
composition and one
or more compounding agents.
[0072] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising: a therapeutic composition comprising therapeutically effective
amounts of azelaic
acid, minoxidil, finasteride, and dutasteride; one or more compounding agents;
and optionally
caffeine and/or saw palmetto extract; wherein formulation comprises a
therapeutically effective
amount of azelaic acid, minoxidil, finasteride, and dutasteride; and the
formulation comprises
ethoxy glycol in an amount of about 1.0 wt%, about 1.1 wt%, about 1.2 wt%,
about 1.3 wt%,
about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%,
about 1.9 wt%,
about 2.0 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%,
about 2.5 wt%,
about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%,
about 3.1 wt%,
about 3.2 wt%, about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%,
about 3.7 wt%,
about 3.8 wt%, about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%,
about 4.3 wt%,
about 4.4 wt%, about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%,
about 4.9 wt%,
about 5.0 wt%, about 5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%,
about 5.5 wt%,
about 5.6 wt%, about 5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%,
about 6.1 wt%,
about 6.2 wt%, about 6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6 wt%,
about 6.7 wt%,
about 6.8 wt%, about 6.9 wt%, about 7.0 wt%, about 7.1 wt%, about 7.2 wt%,
about 7.3 wt%,
about 7.4 wt%, about 7.5 wt%, about 7.6 wt%, about 7.7 wt%, about 7.8 wt%,
about 7.9 wt%,
about 8.0 wt%, about 8.1 wt%, about 8.2 wt%, about 8.3 vvt%, about 8.4 wt%,
about 8.5 wt%,
about 8.6 wt%, about 8.7 wt%, about 8.8 wt%, about 8.9 wt%, about 9.0 wt%,
about 9.1 wt%,
about 9.2 wt%, about 9.3 wt%, about 9.4 wt%, about 9.5 wt%, about 9.6 wt%,
about 9.7 wt%,
about 9.8 wt%, about 9.9 wt%, about 10.0 wt%; or any range encompassed by the
foregoing
values; or any combination of the foregoing values.
[0073] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising: a therapeutic composition comprising therapeutically effective
amounts of azelaic
acid, minoxidil, finasteride, and dutasteride; one or more compounding agents;
and optionally
caffeine and/or saw palmetto extract; wherein formulation comprises a
therapeutically effective
amount of azelaic acid, minoxidil, finasteride, and dutasteride; and the
formulation comprises
propylene glycol in an amount of about 1.0 wt%, about 1.1 wt%, about 1.2 wt%,
about 1.3 wt%,
about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%,
about 1.9 wt%,
26
Date Recue/Date Received 2023-08-18
about 2.0 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%,
about 2.5 wt%,
about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%,
about 3.1 wt%,
about 3.2 wt%, about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%,
about 3.7 wt%,
about 3.8 wt%, about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%,
about 4.3 wt%,
about 4.4 wt%, about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%,
about 4.9 wt%,
about 5.0 wt%, about 5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%,
about 5.5 wt%,
about 5.6 wt%, about 5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%,
about 6.1 wt%,
about 6.2 wt%, about 6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6 wt%,
about 6.7 wt%,
about 6.8 wt%, about 6.9 wt%, about 7.0 wt%, about 7.1 wt%, about 7.2 wt%,
about 7.3 wt%,
about 7.4 wt%, about 7.5 wt%, about 7.6 wt%, about 7.7 vvt%, about 7.8 wt%,
about 7.9 wt%,
about 8.0 wt%, about 8.1 wt%, about 8.2 wt%, about 8.3 wt%, about 8.4 wt%,
about 8.5 wt%,
about 8.6 wt%, about 8.7 wt%, about 8.8 wt%, about 8.9 wt%, about 9.0 wt%,
about 9.1 wt%,
about 9.2 wt%, about 9.3 wt%, about 9.4 wt%, about 9.5 wt%, about 9.6 wt%,
about 9.7 wt%,
about 9.8 wt%, about 9.9 wt%, about 10.0 wt%; or any range encompassed by the
foregoing
values; or any combination of the foregoing values.
[0074] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising: a therapeutic composition comprising therapeutically effective
amounts of azelaic
acid, minoxidil, finasteride, and dutasteride; one or more compounding agents;
and optionally
caffeine and/or saw palmetto extract; wherein formulation comprises a
therapeutically effective
amount of azelaic acid, minoxidil, finasteride, and dutasteride; and the
formulation comprises a
gel base for gel-cream emulsions in an amount of about 5.0 wt%, about 5.1 wt%,
about 5.2
wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%, about 5.6 wt%, about 5.7
wt%, about 5.8
wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%, about 6.2 wt%, about 6.3
wt%, about 6.4
wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%, about 6.8 wt%, about 6.9
wt%, about 7.0
wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%, about 7.4 wt%, about 7.5
vvt%, about 7.6
wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%, about 8.0 wt%, about 8.1
wt%, about 8.2
wt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%, about 8.6 wt%, about 8.7
wt%, about 8.8
wt%, about 8.9 wt%, about 9.0 wt%, about 9.1 wt%, about 9.2 wt%, about 9.3
wt%, about 9.4
wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%, about 9.8 wt%, about 9.9
wt%, about 10.0
wt%, about 10.1 wt%, about 10.2 wt%, about 10.3 wt%, about 10.4 wt%, about
10.5 wt%, about
10.6 wt%, about 10.7 wt%, about 10.8 wt%, about 10.9 wt%, about 11.0 wt%,
about 11.1 wt%,
about 11.2 wt%, about 11.3 wt%, about 11.4 wt%, about 11.5 wt%, about 11.6
wt%, about 11.7
wt%, about 11.8 wt%, about 11.9 wt%, about 12.0 wt%, about 12.1 wt%, about
12.2 wt%, about
27
Date Recue/Date Received 2023-08-18
12.3 wt%, about 12.4 wt%, about 12.5 wt%, about 12.6 wt%, about 12.7 wt%,
about 12.8 wt%,
about 12.9 wt%, about 13.0 wt%, about 13.1 wt%, about 13.2 wt%, about 13.3
wt%, about 13.4
wt%, about 13.5 wt%, about 13.6 wt%, about 13.7 wt%, about 13.8 wt%, about
13.9 wt%, about
14.0 wt%, about 14.1 vvt%, about 14.2 wt%, about 14.3 wt%, about 14.4 wt%,
about 14.5 wt%,
about 14.6 wt%, about 14.7 wt%, about 14.8 wt%, about 14.9 wt%, about 15.0
wt%, about 15.1
wt%, about 15.2 wt%, about 15.3 wt%, about 15.4 wt%, about 15.5 wt%, about
15.6 wt%, about
15.7 wt%, about 15.8 wt%, about 15.9 wt%, about 16.0 wt%, about 16.1 wt%,
about 16.2 wt%,
about 16.3 wt%, about 16.4 wt%, about 16.5 wt%, about 16.6 wt%, about 16.7
wt%, about 16.8
wt%, about 16.9 wt%, about 17.0 wt%, about 17.1 wt%, about 17.2 wt%, about
17.3 wt%, about
17.4 wt%, about 17.5 wt%, about 17.6 wt%, about 17.7 wt%, about 17.8 wt%,
about 17.9 wt%,
about 18.0 wt%, about 18.1 wt%, about 18.2 wt%, about 18.3 wt%, about 18.4
wt%, about 18.5
wt%, about 18.6 wt%, about 18.7 wt%, about 18.8 wt%, about 18.9 wt%, about
19.0 wt%, about
19.1 wt%, about 19.2 wt%, about 19.3 wt%, about 19.4 wt%, about 19.5 wt%,
about 19.6 wt%,
about 19.7 wt%, about 19.8 wt%, about 19.9 wt%, about 20.0 wt%; or any range
encompassed
by the foregoing values; or any combination of the foregoing values.
[0075] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising: a therapeutic composition comprising therapeutically effective
amounts of azelaic
acid, minoxidil, finasteride, and dutasteride; one or more compounding agents;
and optionally
caffeine and/or saw palmetto extract; wherein formulation comprises a
therapeutically effective
amount of azelaic acid, minoxidil, finasteride, and dutasteride; and the
formulation comprises a
cream base in an amount of about 15.0 wt%, about 15.1 wt%, about 15.2 wt%,
about 15.3 wt%,
about 15.4 wt%, about 15.5 wt%, about 15.6 wt%, about 15.7 wt%, about 15.8
wt%, about 15.9
wt%, about 16.0 wt%, about 16.1 wt%, about 16.2 wt%, about 16.3 wt%, about
16.4 wt%, about
16.5 wt%, about 16.6 wt%, about 16.7 wt%, about 16.8 wt%, about 16.9 wt%,
about 17.0 wt%,
about 17.1 wt%, about 17.2 wt%, about 17.3 wt%, about 17.4 wt%, about 17.5
wt%, about 17.6
wt%, about 17.7 wt%, about 17.8 wt%, about 17.9 wt%, about 18.0 wt%, about
18.1 wt%, about
18.2 wt%, about 18.3 wt%, about 18.4 wt%, about 18.5 wt%, about 18.6 wt%,
about 18.7 wt%,
about 18.8 wt%, about 18.9 wt%, about 19.0 wt%, about 19.1 wt%, about 19.2
wt%, about 19.3
wt%, about 19.4 wt%, about 19.5 wt%, about 19.6 wt%, about 19.7 wt%, about
19.8 wt%, about
19.9 wt%, about 20.0 wt%, about 20.1 wt%, about 20.2 wt%, about 20.3 wt%,
about 20.4 wt%,
about 20.5 wt%, about 20.6 wt%, about 20.7 wt%, about 20.8 wt%, about 20.9
wt%, about 21.0
wt%, about 21.1 wt%, about 21.2 wt%, about 21.3 wt%, about 21.4 wt%, about
21.5 wt%, about
21.6 wt%, about 21.7 wt%, about 21.8 wt%, about 21.9 wt%, about 22.0 wt%,
about 22.1 wt%,
28
Date Recue/Date Received 2023-08-18
about 22.2 wt%, about 22.3 wt%, about 22.4 wt%, about 22.5 wt%, about 22.6
wt%, about 22.7
wt%, about 22.8 wt%, about 22.9 wt%, about 23.0 wt%, about 23.1 wt%, about
23.2 wt%, about
23.3 wt%, about 23.4 wt%, about 23.5 wt%, about 23.6 wt%, about 23.7 wt%,
about 23.8 wt%,
about 23.9 wt%, about 24.0 wt%, about 24.1 wt%, about 24.2 wt%, about 24.3
wt%, about 24.4
wt%, about 24.5 wt%, about 24.6 wt%, about 24.7 wt%, about 24.8 wt%, about
24.9 wt%, about
25.0 wt%, about 25.1 wt%, about 25.2 wt%, about 25.3 wt%, about 25.4 wt%,
about 25.5 wt%,
about 25.6 wt%, about 25.7 wt%, about 25.8 wt%, about 25.9 wt%, about 26.0
wt%, about 26.1
wt%, about 26.2 wt%, about 26.3 wt%, about 26.4 wt%, about 26.5 wt%, about
26.6 wt%, about
26.7 wt%, about 26.8 wt%, about 26.9 wt%, about 27.0 wt%, about 27.1 wt%,
about 27.2 wt%,
about 27.3 wt%, about 27.4 wt%, about 27.5 wt%, about 27.6 wt%, about 27.7
wt%, about 27.8
wt%, about 27.9 wt%, about 28.0 wt%, about 28.1 wt%, about 28.2 wt%, about
28.3 wt%, about
28.4 wt%, about 28.5 wt%, about 28.6 wt%, about 28.7 wt%, about 28.8 wt%,
about 28.9 wt%,
about 29.0 wt%, about 29.1 wt%, about 29.2 wt%, about 29.3 wt%, about 29.4
wt%, about 29.5
wt%, about 29.6 wt%, about 29.7 wt%, about 29.8 wt%, about 29.9 wt%, about
30.0 wt%, about
30.1 wt%, about 30.2 wt%, about 30.3 wt%, about 30.4 wt%, about 30.5 wt%,
about 30.6 wt%,
about 30.7 wt%, about 30.8 wt%, about 30.9 wt%, about 31.0 wt%, about 31.1
wt%, about 31.2
wt%, about 31.3 wt%, about 31.4 wt%, about 31.5 wt%, about 31.6 wt%, about
31.7 wt%, about
31.8 wt%, about 31.9 wt%, about 32.0 wt%, about 32.1 wt%, about 32.2 wt%,
about 32.3 wt%,
about 32.4 wt%, about 32.5 wt%, about 32.6 wt%, about 32.7 wt%, about 32.8
wt%, about 32.9
wt%, about 33.0 wt%, about 33.1 wt%, about 33.2 wt%, about 33.3 wt%, about
33.4 wt%, about
33.5 wt%, about 33.6 wt%, about 33.7 wt%, about 33.8 wt%, about 33.9 wt%,
about 34.0 wt%,
about 34.1 wt%, about 34.2 wt%, about 34.3 wt%, about 34.4 wt%, about 34.5
wt%, about 34.6
wt%, about 34.7 wt%, about 34.8 wt%, about 34.9 wt%, about 35.0 wt%; or any
range
encompassed by the foregoing values; or any combination of the foregoing
values.
[0076] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising: a therapeutic composition comprising therapeutically effective
amounts of azelaic
acid, minoxidil, finasteride, and dutasteride; one or more compounding agents;
and optionally
caffeine and/or saw palmetto extract; wherein formulation comprises a
therapeutically effective
amount of azelaic acid, minoxidil, finasteride, and dutasteride; and the
formulation comprises a
silicone base in an amount of about 15.0 wt%, about 15.1 wt%, about 15.2 wt%,
about 15.3
wt%, about 15.4 wt%, about 15.5 wt%, about 15.6 wt%, about 15.7 wt%, about
15.8 wt%, about
15.9 wt%, about 16.0 wt%, about 16.1 wt%, about 16.2 wt%, about 16.3 wt%,
about 16.4 wt%,
about 16.5 wt%, about 16.6 wt%, about 16.7 wt%, about 16.8 wt%, about 16.9
wt%, about 17.0
29
Date Recue/Date Received 2023-08-18
wt%, about 17.1 wt%, about 17.2 wt%, about 17.3 wt%, about 17.4 wt%, about
17.5 wt%, about
17.6 wt%, about 17.7 wt%, about 17.8 wt%, about 17.9 wt%, about 18.0 wt%,
about 18.1 wt%,
about 18.2 wt%, about 18.3 wt%, about 18.4 wt%, about 18.5 wt%, about 18.6
wt%, about 18.7
wt%, about 18.8 wt%, about 18.9 wt%, about 19.0 wt%, about 19.1 wt%, about
19.2 wt%, about
19.3 wt%, about 19.4 wt%, about 19.5 wt%, about 19.6 wt%, about 19.7 wt%,
about 19.8 wt%,
about 19.9 wt%, about 20.0 wt%, about 20.1 wt%, about 20.2 wt%, about 20.3
wt%, about 20.4
wt%, about 20.5 wt%, about 20.6 wt%, about 20.7 wt%, about 20.8 wt%, about
20.9 wt%, about
21.0 wt%, about 21.1 wt%, about 21.2 wt%, about 21.3 wt%, about 21.4 wt%,
about 21.5 wt%,
about 21.6 wt%, about 21.7 wt%, about 21.8 wt%, about 21.9 wt%, about 22.0
wt%, about 22.1
wt%, about 22.2 wt%, about 22.3 wt%, about 22.4 wt%, about 22.5 wt%, about
22.6 wt%, about
22.7 wt%, about 22.8 wt%, about 22.9 wt%, about 23.0 wt%, about 23.1 wt%,
about 23.2 wt%,
about 23.3 wt%, about 23.4 wt%, about 23.5 wt%, about 23.6 wt%, about 23.7
wt%, about 23.8
wt%, about 23.9 wt%, about 24.0 wt%, about 24.1 wt%, about 24.2 wt%, about
24.3 wt%, about
24.4 wt%, about 24.5 wt%, about 24.6 wt%, about 24.7 wt%, about 24.8 wt%,
about 24.9 wt%,
about 25.0 wt%, about 25.1 wt%, about 25.2 wt%, about 25.3 wt%, about 25.4
wt%, about 25.5
wt%, about 25.6 wt%, about 25.7 wt%, about 25.8 wt%, about 25.9 wt%, about
26.0 wt%, about
26.1 wt%, about 26.2 wt%, about 26.3 wt%, about 26.4 wt%, about 26.5 wt%,
about 26.6 wt%,
about 26.7 wt%, about 26.8 wt%, about 26.9 wt%, about 27.0 wt%, about 27.1
wt%, about 27.2
wt%, about 27.3 wt%, about 27.4 wt%, about 27.5 wt%, about 27.6 wt%, about
27.7 wt%, about
27.8 wt%, about 27.9 wt%, about 28.0 wt%, about 28.1 wt%, about 28.2 wt%,
about 28.3 wt%,
about 28.4 wt%, about 28.5 wt%, about 28.6 wt%, about 28.7 wt%, about 28.8
wt%, about 28.9
wt%, about 29.0 wt%, about 29.1 wt%, about 29.2 wt%, about 29.3 wt%, about
29.4 wt%, about
29.5 wt%, about 29.6 wt%, about 29.7 wt%, about 29.8 wt%, about 29.9 wt%,
about 30.0 wt%,
about 30.1 wt%, about 30.2 wt%, about 30.3 wt%, about 30.4 wt%, about 30.5
wt%, about 30.6
wt%, about 30.7 wt%, about 30.8 wt%, about 30.9 wt%, about 31.0 wt%, about
31.1 wt%, about
31.2 wt%, about 31.3 wt%, about 31.4 wt%, about 31.5 wt%, about 31.6 wt%,
about 31.7 wt%,
about 31.8 wt%, about 31.9 wt%, about 32.0 wt%, about 32.1 wt%, about 32.2
wt%, about 32.3
wt%, about 32.4 wt%, about 32.5 wt%, about 32.6 wt%, about 32.7 wt%, about
32.8 wt%, about
32.9 wt%, about 33.0 wt%, about 33.1 wt%, about 33.2 wt%, about 33.3 wt%,
about 33.4 wt%,
about 33.5 wt%, about 33.6 wt%, about 33.7 wt%, about 33.8 wt%, about 33.9
wt%, about 34.0
wt%, about 34.1 wt%, about 34.2 wt%, about 34.3 wt%, about 34.4 wt%, about
34.5 wt%, about
34.6 wt%, about 34.7 wt%, about 34.8 wt%, about 34.9 wt%, about 35.0 wt%,
about 35.1 wt%,
about 35.2 wt%, about 35.3 wt%, about 35.4 wt%, about 35.5 wt%, about 35.6
wt%, about 35.7
wt%, about 35.8 wt%, about 35.9 wt%, about 36.0 wt%, about 36.1 wt%, about
36.2 wt%, about
Date Recue/Date Received 2023-08-18
36.3 wt%, about 36.4 wt%, about 36.5 wt%, about 36.6 wt%, about 36.7 wt%,
about 36.8 wt%,
about 36.9 wt%, about 37.0 wt%, about 37.1 wt%, about 37.2 wt%, about 37.3
wt%, about 37.4
wt%, about 37.5 wt%, about 37.6 wt%, about 37.7 wt%, about 37.8 wt%, about
37.9 wt%, about
38.0 wt%, about 38.1 wt%, about 38.2 wt%, about 38.3 wt%, about 38.4 wt%,
about 38.5 wt%,
about 38.6 wt%, about 38.7 wt%, about 38.8 wt%, about 38.9 wt%, about 39.0
wt%, about 39.1
wt%, about 39.2 wt%, about 39.3 wt%, about 39.4 wt%, about 39.5 wt%, about
39.6 wt%, about
39.7 wt%, about 39.8 wt%, about 39.9 wt%, about 40.0 wt%, about 40.1 wt%,
about 40.2 wt%,
about 40.3 wt%, about 40.4 wt%, about 40.5 wt%, about 40.6 wt%, about 40.7
wt%, about 40.8
wt%, about 40.9 wt%, about 41.0 wt%, about 41.1 wt%, about 41.2 wt%, about
41.3 wt%, about
41.4 wt%, about 41.5 wt%, about 41.6 wt%, about 41.7 wt%, about 41.8 wt%,
about 41.9 wt%,
about 42.0 wt%, about 42.1 wt%, about 42.2 wt%, about 42.3 wt%, about 42.4
wt%, about 42.5
wt%, about 42.6 wt%, about 42.7 wt%, about 42.8 wt%, about 42.9 wt%, about
43.0 wt%, about
43.1 wt%, about 43.2 wt%, about 43.3 wt%, about 43.4 wt%, about 43.5 wt%,
about 43.6 wt%,
about 43.7 wt%, about 43.8 wt%, about 43.9 wt%, about 44.0 wt%, about 44.1
wt%, about 44.2
wt%, about 44.3 wt%, about 44.4 wt%, about 44.5 wt%, about 44.6 wt%, about
44.7 wt%, about
44.8 wt%, about 44.9 wt%, about 45.0 wt%, about 45.1 wt%, about 45.2 wt%,
about 45.3 wt%,
about 45.4 wt%, about 45.5 wt%, about 45.6 wt%, about 45.7 wt%, about 45.8
wt%, about 45.9
wt%, about 46.0 wt%, about 46.1 wt%, about 46.2 wt%, about 46.3 wt%, about
46.4 wt%, about
46.5 wt%, about 46.6 wt%, about 46.7 wt%, about 46.8 wt%, about 46.9 wt%,
about 47.0 wt%,
about 47.1 wt%, about 47.2 wt%, about 47.3 wt%, about 47.4 wt%, about 47.5
wt%, about 47.6
wt%, about 47.7 wt%, about 47.8 wt%, about 47.9 wt%, about 48.0 wt%, about
48.1 wt%, about
48.2 wt%, about 48.3 wt%, about 48.4 wt%, about 48.5 wt%, about 48.6 wt%,
about 48.7 wt%,
about 48.8 wt%, about 48.9 wt%, about 49.0 wt%, about 49.1 wt%, about 49.2
wt%, about 49.3
wt%, about 49.4 wt%, about 49.5 wt%, about 49.6 wt%, about 49.7 wt%, about
49.8 wt%, about
49.9 wt%, about 50.0 wt%; or any range encompassed by the foregoing values; or
any
combination of the foregoing values.
[0077] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising: a therapeutic composition comprising therapeutically effective
amounts of azelaic
acid, minoxidil, finasteride, and dutasteride; one or more compounding agents;
and optionally
caffeine and/or saw palmetto extract; wherein formulation comprises a
therapeutically effective
amount of azelaic acid, minoxidil, finasteride, and dutasteride; wherein the
formulation
comprises one or more compounding agent in a disclosed amount; and wherein the
formulation
comprises caffeine present in an amount of about 0.00010 wt%, about 0.00015
wt%, about
31
Date Recue/Date Received 2023-08-18
0.00020 wt%, about 0.0025 wt%, about 0.00030 wt%, about 0.00035 wt%, about
0.00040 wt%,
about 0.00045 wt%, about 0.00050 wt%, about 0.00055 wt%, about 0.00060 wt%,
about
0.00065 wt%, about 0.00070 wt%, about 0.00075 wt%, about 0.00080 wt%, about
0.00085 wt%,
about 0.00090 wt%, about 0.00095 wt%, about 0.00100 wt%, about 0.00105 wt%,
about
0.00110 wt%, about 0.00115 wt%, about 0.00120 wt%, about 0.00125 wt%, about
0.00130 wt%,
about 0.00135 wt%, about 0.00140 wt%, about 0.00145 wt%, about 0.00150 wt%,
about
0.00155 wt%, about 0.00160 wt%, about 0.00165 wt%, about 0.00170 wt%, about
0.00175 wt%,
about 0.00180 wt%, about 0.00185 wt%, about 0.00190 wt%, about 0.00195
wt%,about 0.0020
wt%, about 0.0025 wt%, about 0.0030 wt%, about 0.0035 wt%, about 0.0040 wt%,
about 0.0045
wt%, about 0.0050 wt%, about 0.0055 wt%, about 0.0060 wt%, about 0.0065 wt%,
about 0.0070
wt%; or any range encompassed by the foregoing values; or any combination of
the foregoing
values.
[0078] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising: a therapeutic composition comprising therapeutically effective
amounts of azelaic
acid, minoxidil, finasteride, and dutasteride; one or more compounding agents;
and optionally
caffeine and/or saw palmetto extract; wherein formulation comprises a
therapeutically effective
amount of azelaic acid, minoxidil, finasteride, and dutasteride; wherein the
formulation
comprises one or more compounding agent in a disclosed amount; and wherein the
formulation
comprises saw palmetto extract present in an amount of about 0.10 wt%, about
0.20 wt%, about
0.30 wt%, about 0.40 wt%, about 0.50 wt%, about 0.60 wt%, about 0.70 wt%,
about 0.80 wt%,
about 0.90 wt%, about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%,
about 1.4 wt%,
about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%,
about 2.0 wt%,
about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%,
about 2.6 wt%,
about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%,
about 3.2 wt%,
about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%,
about 3.8 wt%,
about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%,
about 4.4 wt%,
about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%,
about 5.0 wt%,
about 5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%,
about 5.6 wt%,
about 5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%,
about 6.2 wt%,
about 6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%,
about 6.8 wt%,
about 6.9 wt%, about 7.0 wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%,
about 7.4 wt%,
about 7.5 wt%, about 7.6 wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%,
about 8.0 wt%,
about 8.1 wt%, about 8.2 wt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%,
about 8.6 wt%,
32
Date Recue/Date Received 2023-08-18
about 8.7 wt%, about 8.8 wt%, about 8.9 wt%, about 9.0 wt%, about 9.1 wt%,
about 9.2 wt%,
about 9.3 wt%, about 9.4 wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%,
about 9.8 wt%,
about 9.9 wt%, about 10.0 wt%, about 10.1 wt%, about 10.2 wt%, about 10.3 wt%,
about 10.4
wt%, about 10.5 wt%, about 10.6 wt%, about 10.7 wt%, about 10.8 wt%, about
10.9 wt%, about
11.0 wt%, about 11.1 wt%, about 11.2 wt%, about 11.3 wt%, about 11.4 wt%,
about 11.5 wt%,
about 11.6 wt%, about 11.7 wt%, about 11.8 wt%, about 11.9 wt%, about 12.0
wt%, about 12.1
wt%, about 12.2 wt%, about 12.3 wt%, about 12.4 wt%, about 12.5 wt%, about
12.6 wt%, about
12.7 wt%, about 12.8 wt%, about 12.9 wt%, about 13.0 wt%, about 13.1 wt%,
about 13.2 wt%,
about 13.3 wt%, about 13.4 wt%, about 13.5 wt%, about 13.6 wt%, about 13.7
wt%, about 13.8
wt%, about 13.9 wt%, about 14.0 wt%, about 14.1 wt%, about 14.2 wt%, about
14.3 wt%, about
14.4 wt%, about 14.5 wt%, about 14.6 wt%, about 14.7 wt%, about 14.8 wt%,
about 14.9 wt%,
about 15.0 wt%; or any range encompassed by the foregoing values; or any
combination of the
foregoing values.
[0079] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising: a therapeutic composition comprising therapeutically effective
amounts of azelaic
acid, minoxidil, finasteride, and dutasteride; one or more compounding agents;
and optionally
caffeine and/or saw palmetto extract; wherein formulation comprises a
therapeutically effective
amount of azelaic acid, minoxidil, finasteride, and dutasteride; wherein the
formulation
comprises one or more compounding agent in a disclosed amount; wherein the
formulation
comprises caffeine present in an amount of about 0.00010 wt%, about 0.00015
wt%, about
0.00020 wt%, about 0.0025 wt%, about 0.00030 wt%, about 0.00035 wt%, about
0.00040 wt%,
about 0.00045 wt%, about 0.00050 wt%, about 0.00055 wt%, about 0.00060 wt%,
about
0.00065 wt%, about 0.00070 wt%, about 0.00075 wt%, about 0.00080 wt%, about
0.00085 wt%,
about 0.00090 wt%, about 0.00095 wt%, about 0.00100 wt%, about 0.00105 wt%,
about
0.00110 wt%, about 0.00115 wt%, about 0.00120 wt%, about 0.00125 wV/0, about
0.00130 wt%,
about 0.00135 wt%, about 0.00140 wt%, about 0.00145 wt%, about 0.00150 wt%,
about
0.00155 wt%, about 0.00160 wt%, about 0.00165 wt%, about 0.00170 wt%, about
0.00175 wt%,
about 0.00180 wt%, about 0.00185 wt%, about 0.00190 wt%, about 0.00195
wt%,about 0.0020
wt%, about 0.0025 wt%, about 0.0030 wt%, about 0.0035 wt%, about 0.0040 wt%,
about 0.0045
wt%, about 0.0050 wt%, about 0.0055 wt%, about 0.0060 wt%, about 0.0065 wt%,
about 0.0070
wt%; or any range encompassed by the foregoing values; or any combination of
the foregoing
values; and wherein the formulation comprises saw palmetto extract present in
an amount of
about 0.10 wt%, about 0.20 wt%, about 0.30 wt%, about 0.40 wt%, about 0.50
wt%, about 0.60
33
Date Recue/Date Received 2023-08-18
wt%, about 0.70 wt%, about 0.80 wt%, about 0.90 wt%, about 1.0 wt%, about 1.1
wt%, about
1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7
wt%, about
1.8 wt%, about 1.9 wt%, about 2.0 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3
wt%, about
2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9
wt%, about
3.0 wt%, about 3.1 wt%, about 3.2 wt%, about 3.3 wt%, about 3.4 wt%, about 3.5
wt%, about
3.6 wt%, about 3.7 wt%, about 3.8 wt%, about 3.9 wt%, about 4.0 wt%, about 4.1
wt%, about
4.2 wt%, about 4.3 wt%, about 4.4 wt%, about 4.5 wt%, about 4.6 wt%, about 4.7
wt%, about
4.8 wt%, about 4.9 wt%, about 5.0 wt%, about 5.1 wt%, about 5.2 wt%, about 5.3
wt%, about
5.4 wt%, about 5.5 wt%, about 5.6 wt%, about 5.7 wt%, about 5.8 wt%, about 5.9
wt%, about
6.0 wt%, about 6.1 wt%, about 6.2 wt%, about 6.3 wt%, about 6.4 wt%, about 6.5
wt%, about
6.6 wt%, about 6.7 wt%, about 6.8 wt%, about 6.9 wt%, about 7.0 wt%, about 7.1
wt%, about
7.2 wt%, about 7.3 wt%, about 7.4 wt%, about 7.5 wt%, about 7.6 wt%, about 7.7
wt%, about
7.8 wt%, about 7.9 wt%, about 8.0 wt%, about 8.1 wt%, about 8.2 wt%, about 8.3
wt%, about
8.4 wt%, about 8.5 wt%, about 8.6 wt%, about 8.7 wt%, about 8.8 wt%, about 8.9
wt%, about
9.0 wt%, about 9.1 wt%, about 9.2 wt%, about 9.3 wt%, about 9.4 wt%, about 9.5
wt%, about
9.6 wt%, about 9.7 wt%, about 9.8 wt%, about 9.9 wt%, about 10.0 wt%, about
10.1 wt%, about
10.2 wt%, about 10.3 wt%, about 10.4 wt%, about 10.5 wt%, about 10.6 wt%,
about 10.7 wt%,
about 10.8 wt%, about 10.9 wt%, about 11.0 wt%, about 11.1 wt%, about 11.2
wt%, about 11.3
wt%, about 11.4 wt%, about 11.5 wt%, about 11.6 wt%, about 11.7 wt%, about
11.8 wt%, about
11.9 wt%, about 12.0 wt%, about 12.1 wt%, about 12.2 wt%, about 12.3 wt%,
about 12.4 wt%,
about 12.5 wt%, about 12.6 wt%, about 12.7 wt%, about 12.8 wt%, about 12.9
wt%, about 13.0
wt%, about 13.1 wt%, about 13.2 wt%, about 13.3 wt%, about 13.4 wt%, about
13.5 wt%, about
13.6 wt%, about 13.7 wt%, about 13.8 wt%, about 13.9 wt%, about 14.0 wt%,
about 14.1 wt%,
about 14.2 wt%, about 14.3 wt%, about 14.4 wt%, about 14.5 wt%, about 14.6
wt%, about 14.7
wt%, about 14.8 wt%, about 14.9 wt%, about 15.0 wt%; or any range encompassed
by the
foregoing values; or any combination of the foregoing values.
[0080] In a further aspect, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising therapeutically effective amounts of azelaic acid and
minoxidil; one or
more compounding agents; and optionally caffeine and/or saw palmetto extract.
[0081] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid and minoxidil; one or more compounding agents; and
optionally
caffeine and/or saw palmetto extract; wherein the formulation comprises
therapeutically
34
Date Recue/Date Received 2023-08-18
effective amounts of azelaic acid and minoxidil as follows: about 0.100 wt% to
about 0.500 wt%
azelaic acid; and about 10 wt% to about 20 wt% minoxidil; wherein the wt% of a
component is
based on the total weight of the therapeutic composition; and one or more
compound agents.
[0082] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid and minoxidil; one or more compounding agents; and
optionally
caffeine and/or saw palmetto extract; wherein the formulation comprises
therapeutically
effective amounts of azelaic acid and minoxidil as follows: about 0.300 wt% to
about 0.400 wt%
azelaic acid; and about 12 wt% to about 17 wt% minoxidil; wherein the wt% of a
component is
based on the total weight of the therapeutic composition; and one or more
compounding agents.
[0083] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid and minoxidil; one or more compounding agents; and
optionally
caffeine and/or saw palmetto extract; wherein the formulation comprises
therapeutically
effective amounts of azelaic acid, minoxidil, finasteride, and dutasteride as
follows: about 0.325
wt% azelaic acid and about 15 wt% minoxidil; wherein the wt% of a component is
based on the
total weight of the therapeutic composition and one or more compounding
agents.
[0084] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid and minoxidil; one or more compounding agents; and
optionally
caffeine and/or saw palmetto extract; wherein the azelaic acid is present in
an amount of about
0.100 wt%, about 0.105 wt%, about 0.110 wt%, about 0.115 wt%, about 0.120 wt%,
about 0.125
wt%, about 0.130 wt%, about 0.135 wt%, about 0.140 wt%, about 0.145 wt%, about
0.150 wt%,
about 0.155 wt%, about 0.160 wt%, about 0.165 wt%, about 0.170 wt%, about
0.175 wt%, about
0.180 wt%, about 0.185 wt%, about 0.190 wt%, about 0.195 wt%, about 0.200 wt%,
about 0.205
wt%, about 0.210 wt%, about 0.215 wt%, about 0.220 wt%, about 0.225 wt%, about
0.230 wt%,
about 0.235 wt%, about 0.240 wt%, about 0.245 wt%, about 0.250 wt%, about
0.255 wt%, about
0.260 wt%, about 0.265 wt%, about 0.270 wt%, about 0.275 wt%, about 0.280 wt%,
about 0.285
wt%, about 0.290 wt%, about 0.295 wt%, about 0.300 wt%, about 0.305 wt%, about
0.310 wt%,
about 0.315 wt%, about 0.320 wt%, about 0.325 wt%, about 0.330 wt%, about
0.335 wt%, about
0.340 wt%, about 0.345 wt%, about 0.350 wt%, about 0.355 wt%, about 0.360 wt%,
about 0.365
wt%, about 0.370 wt%, about 0.375 wt%, about 0.380 wt%, about 0.385 wt%, about
0.390 wt%,
about 0.395 wt%, about 0.400 wt%, about 0.405 wt%, about 0.410 wt%, about
0.415 wt%, about
0.420 wt%, about 0.425 wt%, about 0.430 wt%, about 0.435 wt%, about 0.440 wt%,
about 0.445
wt%, about 0.450 wt%, about 0.455 wt%, about 0.460 wt%, about 0.465 wt%, about
0.470 wt%,
about 0.475 wt%, about 0.480 wt%, about 0.485 wt%, about 0.490 wt%, about
0.495 wt%, about
Date Recue/Date Received 2023-08-18
0.500 wt%; or any range encompassed by the foregoing values; or any
combination of the
foregoing values.
[0085] In a further aspect, the disclosed topical formulation comprising
therapeutically effective
amounts of azelaic acid and minoxidil; one or more compounding agents; and
optionally
caffeine and/or saw palmetto extract; wherein the minoxidil is present in an
amount of about 1.0
wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5
wt%, about 1.6
wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2.0 wt%, about 2.1
wt%, about 2.2
wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7
wt%, about 2.8
wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%, about 3.2 wt%, about 3.3
wt%, about 3.4
wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%, about 3.8 wt%, about 3.9
wt%, about 4.0
wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%, about 4.4 wt%, about 4.5
wt%, about 4.6
wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%, about 5.0 wt%, about 5.1
wt%, about 5.2
wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%, about 5.6 wt%, about 5.7
wt%, about 5.8
wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%, about 6.2 wt%, about 6.3
wt%, about 6.4
wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%, about 6.8 wt%, about 6.9
wt%, about 7.0
wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%, about 7.4 wt%, about 7.5
wt%, about 7.6
wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%, about 8.0 wt%, about 8.1
wt%, about 8.2
wt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%, about 8.6 wt%, about 8.7
wt%, about 8.8
wt%, about 8.9 wt%, about 9.0 wt%, about 9.1 wt%, about 9.2 wt%, about 9.3
wt%, about 9.4
wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%, about 9.8 wt%, about 9.9
wt%, about 10.0
wt%, about 10.1 wt%, about 10.2 wt%, about 10.3 wt%, about 10.4 wt%, about
10.5 wt%, about
10.6 wt%, about 10.7 wt%, about 10.8 wt%, about 10.9 wt%, about 11.0 wt%,
about 11.1 wt%,
about 11.2 wt%, about 11.3 wt%, about 11.4 wt%, about 11.5 wt%, about 11.6
wt%, about 11.7
wt%, about 11.8 wt%, about 11.9 wt%, about 12.0 wt%, about 12.1 wt%, about
12.2 wt%, about
12.3 wt%, about 12.4 wt%, about 12.5 wt%, about 12.6 wt%, about 12.7 wt%,
about 12.8 wt%,
about 12.9 wt%, about 13.0 wt%, about 13.1 wt%, about 13.2 wt%, about 13.3
wt%, about 13.4
wt%, about 13.5 wt%, about 13.6 wt%, about 13.7 wt%, about 13.8 wt%, about
13.9 wt%, about
14.0 wt%, about 14.1 wt%, about 14.2 wt%, about 14.3 wt%, about 14.4 wt%,
about 14.5 wt%,
about 14.6 wt%, about 14.7 wt%, about 14.8 wt%, about 14.9 wt%, about 15.0
wt%, about 15.1
wt%, about 15.2 wt%, about 15.3 wt%, about 15.4 wt%, about 15.5 wt%, about
15.6 wt%, about
15.7 wt%, about 15.8 wt%, about 15.9 wt%, about 16.0 wt%, about 16.1 wt%,
about 16.2 wt%,
about 16.3 wt%, about 16.4 wt%, about 16.5 wt%, about 16.6 wt%, about 16.7
wt%, about 16.8
wt%, about 16.9 wt%, about 17.0 wt%, about 17.1 wt%, about 17.2 wt%, about
17.3 wt%, about
17.4 wt%, about 17.5 wt%, about 17.6 wt%, about 17.7 wt%, about 17.8 wt%,
about 17.9 wt%,
36
Date Recue/Date Received 2023-08-18
about 18.0 wt%, about 18.1 wt%, about 18.2 wt%, about 18.3 wt%, about 18.4
wt%, about 18.5
wt%, about 18.6 wt%, about 18.7 wt%, about 18.8 wt%, about 18.9 wt%, about
19.0 wt%, about
19.1 wt%, about 19.2 wt%, about 19.3 wt%, about 19.4 wt%, about 19.5 wt%,
about 19.6 wt%,
about 19.7 wt%, about 19.8 wt%, about 19.9 wt%, about 20.0 wt%; or any range
encompassed
by the foregoing values; or any combination of the foregoing values.
[0086] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising azelaic acid and minoxidil; one or more compounding
agents; and
optionally caffeine and/or saw palmetto extract; wherein the one or more
compounding agents
comprise ethoxy diglycol, propylene glycol, a gel base for gel-cream
emulsions, a cream base, a
silicone base, or combinations thereof.
[0087] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising azelaic acid and minoxidil; one or more compounding
agents; and
optionally caffeine and/or saw palmetto extract; wherein formulation comprises
a therapeutically
effective amount of azelaic acid and minoxidil; and the one or more
compounding agents are
present as follows: about 1 vol/wt% to about 10 vol/wt% ethoxy diglycol; about
1 vol/wt% to
about 10 vol/wt% propylene glycol; about 5 wt% to about 20 wt% of a gel base
for gel-cream
emulsions; about 15 wt% to about 35 wt% of a cream base; and about 15 wt% to
about 50 wt%
of a silicone base; wherein the vvt% of a component is based on the total
weight of the
therapeutic composition and one or more compounding agents; and wherein the
vol/wt% of a
component is based on the total weight of the therapeutic composition and one
or more
compounding agents.
[0088] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising azelaic acid and minoxidil; one or more compounding
agents; and
optionally caffeine and/or saw palmetto extract; wherein formulation comprises
a therapeutically
effective amount of azelaic acid and minoxidil; and the one or more
compounding agents are
present as follows: about 4 vol/wt% to about 6 vol/wt% ethoxy diglycol; about
2.5 vol/wt% to
about 4.5 vol/wt% propylene glycol; about 8 wt% to about 14 wt% of a gel base
for gel-cream
emulsions; about 20 wt% to about 30 wt% of a cream base; and about 20 wt% to
about 30 wt%
of a silicone base; wherein the wt% of a component is based on the total
weight of the
therapeutic composition and one or more compounding agents; and wherein the
vol/wt% of a
37
Date Recue/Date Received 2023-08-18
component is based on the total weight of the therapeutic composition and one
or more
compounding agents.
[0089] In various aspects, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising azelaic acid and minoxidil; one or more compounding
agents; and
optionally caffeine and/or saw palmetto extract; wherein formulation comprises
a therapeutically
effective amount of azelaic acid and minoxidil; and the one or more
compounding agents are
present as follows: about 6 vol/wt% ethoxy diglycol; about 3.5 vol/wt%
propylene glycol; about
11 wt% of a gel base for gel-cream emulsions; about 21 wt% to about 23 wt% of
a cream base;
and about 26 wt% to about 29 wt% of a silicone base; wherein the wt% of a
component is based
on the total weight of the therapeutic composition and one or more compounding
agents; and
wherein the vol/wt% of a component is based on the total weight of the
therapeutic composition
and one or more compounding agents.
[0090] In a further aspect, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising azelaic acid and minoxidil; one or more compounding
agents; and
optionally caffeine and/or saw palmetto extract; wherein formulation comprises
a therapeutically
effective amount of azelaic acid and minoxidil; and the formulation comprises
ethoxy glycol in an
amount of about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about
1.4 wt%, about
1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2.0
wt%, about
2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6
wt%, about
2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%, about 3.2
wt%, about
3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%, about 3.8
wt%, about
3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%, about 4.4
wt%, about
4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%, about 5.0
wt%, about
5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%, about 5.6
wt%, about
5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%, about 6.2
wt%, about
6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%, about 6.8
wt%, about
6.9 wt%, about 7.0 wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%, about 7.4
wt%, about
7.5 wt%, about 7.6 wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%, about 8.0
wt%, about
8.1 wt%, about 8.2 wt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%, about 8.6
wt%, about
8.7 wt%, about 8.8 wt%, about 8.9 wt%, about 9.0 wt%, about 9.1 wt%, about 9.2
wt%, about
9.3 wt%, about 9.4 wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%, about 9.8
wt%, about
38
Date Recue/Date Received 2023-08-18
9.9 wt%, about 10.0 wt%; or any range encompassed by the foregoing values; or
any
combination of the foregoing values.
[0091] In a further aspect, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising azelaic acid and minoxidil; one or more compounding
agents; and
optionally caffeine and/or saw palmetto extract; wherein formulation comprises
a therapeutically
effective amount of azelaic acid and minoxidil; and the formulation comprises
propylene glycol
in an amount of about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%,
about 1.4 wt%,
about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%,
about 2.0 wt%,
about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%,
about 2.6 wt%,
about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%,
about 3.2 wt%,
about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%,
about 3.8 wt%,
about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%,
about 4.4 wt%,
about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%,
about 5.0 wt%,
about 5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%,
about 5.6 wt%,
about 5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%,
about 6.2 wt%,
about 6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%,
about 6.8 wt%,
about 6.9 wt%, about 7.0 wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%,
about 7.4 wt%,
about 7.5 wt%, about 7.6 wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%,
about 8.0 wt%,
about 8.1 wt%, about 8.2 wt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%,
about 8.6 wt%,
about 8.7 wt%, about 8.8 wt%, about 8.9 wt%, about 9.0 vvt%, about 9.1 wt%,
about 9.2 wt%,
about 9.3 wt%, about 9.4 wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%,
about 9.8 wt%,
about 9.9 wt%, about 10.0 wt%; or any range encompassed by the foregoing
values; or any
combination of the foregoing values.
[0092] In a further aspect, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising azelaic acid and minoxidil; one or more compounding
agents; and
optionally caffeine and/or saw palmetto extract; wherein formulation comprises
a therapeutically
effective amount of azelaic acid and minoxidil; and the formulation comprises
a gel base for gel-
cream emulsions in an amount of about 5.0 wt%, about 5.1 wt%, about 5.2 wt%,
about 5.3 wt%,
about 5.4 wt%, about 5.5 wt%, about 5.6 wt%, about 5.7 wt%, about 5.8 wt%,
about 5.9 wt%,
about 6.0 wt%, about 6.1 wt%, about 6.2 wt%, about 6.3 wt%, about 6.4 wt%,
about 6.5 wt%,
about 6.6 wt%, about 6.7 wt%, about 6.8 wt%, about 6.9 wt%, about 7.0 wt%,
about 7.1 wt%,
39
Date Recue/Date Received 2023-08-18
about 7.2 wt%, about 7.3 wt%, about 7.4 wt%, about 7.5 wt%, about 7.6 wt%,
about 7.7 wt%,
about 7.8 wt%, about 7.9 wt%, about 8.0 wt%, about 8.1 wt%, about 8.2 wt%,
about 8.3 wt%,
about 8.4 wt%, about 8.5 wt%, about 8.6 wt%, about 8.7 wt%, about 8.8 wt%,
about 8.9 wt%,
about 9.0 wt%, about 9.1 wt%, about 9.2 wt%, about 9.3 wt%, about 9.4 wt%,
about 9.5 wt%,
about 9.6 wt%, about 9.7 wt%, about 9.8 wt%, about 9.9 wt%, about 10.0 wt%,
about 10.1 wt%,
about 10.2 wt%, about 10.3 wt%, about 10.4 wt%, about 10.5 wt%, about 10.6
wt%, about 10.7
wt%, about 10.8 wt%, about 10.9 wt%, about 11.0 wt%, about 11.1 wt%, about
11.2 wt%, about
11.3 wt%, about 11.4 wt%, about 11.5 wt%, about 11.6 wt%, about 11.7 wt%,
about 11.8 wt%,
about 11.9 wt%, about 12.0 wt%, about 12.1 wt%, about 12.2 wt%, about 12.3
wt%, about 12.4
wt%, about 12.5 wt%, about 12.6 wt%, about 12.7 wt%, about 12.8 wt%, about
12.9 wt%, about
13.0 wt%, about 13.1 wt%, about 13.2 wt%, about 13.3 wt%, about 13.4 wt%,
about 13.5 wt%,
about 13.6 wt%, about 13.7 wt%, about 13.8 wt%, about 13.9 wt%, about 14.0
wt%, about 14.1
wt%, about 14.2 wt%, about 14.3 wt%, about 14.4 wt%, about 14.5 wt%, about
14.6 wt%, about
14.7 wt%, about 14.8 wt%, about 14.9 wt%, about 15.0 wt%, about 15.1 wt%,
about 15.2 wt%,
about 15.3 wt%, about 15.4 wt%, about 15.5 wt%, about 15.6 wt%, about 15.7
wt%, about 15.8
wt%, about 15.9 wt%, about 16.0 wt%, about 16.1 wt%, about 16.2 wt%, about
16.3 wt%, about
16.4 wt%, about 16.5 wt%, about 16.6 wt%, about 16.7 wt%, about 16.8 wt%,
about 16.9 wt%,
about 17.0 wt%, about 17.1 wt%, about 17.2 wt%, about 17.3 wt%, about 17.4
wt%, about 17.5
wt%, about 17.6 wt%, about 17.7 wt%, about 17.8 wt%, about 17.9 wt%, about
18.0 wt%, about
18.1 wt%, about 18.2 wt%, about 18.3 wt%, about 18.4 wt%, about 18.5 wt%,
about 18.6 wt%,
about 18.7 wt%, about 18.8 wt%, about 18.9 wt%, about 19.0 wt%, about 19.1
wt%, about 19.2
wt%, about 19.3 wt%, about 19.4 wt%, about 19.5 wt%, about 19.6 wt%, about
19.7 wt%, about
19.8 wt%, about 19.9 wt%, about 20.0 wt%; or any range encompassed by the
foregoing
values; or any combination of the foregoing values.
[0093] In a further aspect, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
composition comprising azelaic acid and minoxidil; one or more compounding
agents; and
optionally caffeine and/or saw palmetto extract; wherein formulation comprises
a therapeutically
effective amount of azelaic acid and minoxidil; and the formulation comprises
a cream base in
an amount of about 15.0 wt%, about 15.1 wt%, about 15.2 wt%, about 15.3 wt%,
about 15.4
wt%, about 15.5 wt%, about 15.6 wt%, about 15.7 wt%, about 15.8 wt%, about
15.9 wt%, about
16.0 wt%, about 16.1 wt%, about 16.2 wt%, about 16.3 wt%, about 16.4 wt%,
about 16.5 wt%,
about 16.6 wt%, about 16.7 wt%, about 16.8 wt%, about 16.9 wt%, about 17.0
wt%, about 17.1
wt%, about 17.2 wt%, about 17.3 wt%, about 17.4 wt%, about 17.5 wt%, about
17.6 wt%, about
Date Recue/Date Received 2023-08-18
17.7 wt%, about 17.8 wt%, about 17.9 wt%, about 18.0 wt%, about 18.1 wt%,
about 18.2 wt%,
about 18.3 wt%, about 18.4 wt%, about 18.5 wt%, about 18.6 wt%, about 18.7
wt%, about 18.8
wt%, about 18.9 wt%, about 19.0 wt%, about 19.1 wt%, about 19.2 wt%, about
19.3 wt%, about
19.4 wt%, about 19.5 wt%, about 19.6 wt%, about 19.7 wt%, about 19.8 wt%,
about 19.9 wt%,
about 20.0 wt%, about 20.1 wt%, about 20.2 wt%, about 20.3 wt%, about 20.4
wt%, about 20.5
wt%, about 20.6 wt%, about 20.7 wt%, about 20.8 wt%, about 20.9 wt%, about
21.0 wt%, about
21.1 wt%, about 21.2 wt%, about 21.3 wt%, about 21.4 wt%, about 21.5 wt%,
about 21.6 wt%,
about 21.7 wt%, about 21.8 wt%, about 21.9 wt%, about 22.0 wt%, about 22.1
wt%, about 22.2
wt%, about 22.3 wt%, about 22.4 wt%, about 22.5 wt%, about 22.6 wt%, about
22.7 wt%, about
22.8 wt%, about 22.9 wt%, about 23.0 wt%, about 23.1 wt%, about 23.2 wt%,
about 23.3 wt%,
about 23.4 wt%, about 23.5 wt%, about 23.6 wt%, about 23.7 wt%, about 23.8
wt%, about 23.9
wt%, about 24.0 wt%, about 24.1 wt%, about 24.2 wt%, about 24.3 wt%, about
24.4 wt%, about
24.5 wt%, about 24.6 wt%, about 24.7 wt%, about 24.8 wt%, about 24.9 wt%,
about 25.0 wt%,
about 25.1 wt%, about 25.2 wt%, about 25.3 wt%, about 25.4 wt%, about 25.5
wt%, about 25.6
wt%, about 25.7 wt%, about 25.8 wt%, about 25.9 wt%, about 26.0 wt%, about
26.1 wt%, about
26.2 wt%, about 26.3 wt%, about 26.4 wt%, about 26.5 wt%, about 26.6 wt%,
about 26.7 wt%,
about 26.8 wt%, about 26.9 wt%, about 27.0 wt%, about 27.1 wt%, about 27.2
wt%, about 27.3
wt%, about 27.4 wt%, about 27.5 wt%, about 27.6 wt%, about 27.7 wt%, about
27.8 wt%, about
27.9 wt%, about 28.0 wt%, about 28.1 wt%, about 28.2 wt%, about 28.3 wt%,
about 28.4 wt%,
about 28.5 wt%, about 28.6 wt%, about 28.7 wt%, about 28.8 wt%, about 28.9
wt%, about 29.0
wt%, about 29.1 wt%, about 29.2 wt%, about 29.3 wt%, about 29.4 wt%, about
29.5 wt%, about
29.6 wt%, about 29.7 wt%, about 29.8 wt%, about 29.9 wt%, about 30.0 wt%,
about 30.1 wt%,
about 30.2 wt%, about 30.3 wt%, about 30.4 wt%, about 30.5 wt%, about 30.6
wt%, about 30.7
wt%, about 30.8 wt%, about 30.9 wt%, about 31.0 wt%, about 31.1 wt%, about
31.2 wt%, about
31.3 wt%, about 31.4 wt%, about 31.5 wt%, about 31.6 wt%, about 31.7 wt%,
about 31.8 wt%,
about 31.9 wt%, about 32.0 wt%, about 32.1 wt%, about 32.2 wt%, about 32.3
wt%, about 32.4
wt%, about 32.5 wt%, about 32.6 wt%, about 32.7 wt%, about 32.8 wt%, about
32.9 wt%, about
33.0 wt%, about 33.1 wt%, about 33.2 wt%, about 33.3 wt%, about 33.4 wt%,
about 33.5 wt%,
about 33.6 wt%, about 33.7 wt%, about 33.8 wt%, about 33.9 wt%, about 34.0
wt%, about 34.1
wt%, about 34.2 wt%, about 34.3 wt%, about 34.4 wt%, about 34.5 wt%, about
34.6 wt%, about
34.7 wt%, about 34.8 wt%, about 34.9 wt%, about 35.0 wt%; or any range
encompassed by the
foregoing values; or any combination of the foregoing values.
[0094] In a further aspect, the present disclosure pertains to topical
formulations for treatment
of hair loss and/or to increase hair growth, the formulation comprising: a
therapeutic
41
Date Recue/Date Received 2023-08-18
composition comprising azelaic acid and minoxidil; one or more compounding
agents; and
optionally caffeine and/or saw palmetto extract; wherein formulation comprises
a therapeutically
effective amount of azelaic acid and minoxidil; and the formulation comprises
a silicone base in
an amount of about 15.0 wt%, about 15.1 wt%, about 15.2 wt%, about 15.3 wt%,
about 15.4
wt%, about 15.5 wt%, about 15.6 wt%, about 15.7 wt%, about 15.8 wt%, about
15.9 wt%, about
16.0 wt%, about 16.1 wt%, about 16.2 wt%, about 16.3 wt%, about 16.4 wt%,
about 16.5 wt%,
about 16.6 wt%, about 16.7 wt%, about 16.8 wt%, about 16.9 wt%, about 17.0
wt%, about 17.1
wt%, about 17.2 wt%, about 17.3 wt%, about 17.4 wt%, about 17.5 wt%, about
17.6 wt%, about
17.7 wt%, about 17.8 wt%, about 17.9 wt%, about 18.0 wt%, about 18.1 wt%,
about 18.2 wt%,
about 18.3 wt%, about 18.4 wt%, about 18.5 wt%, about 18.6 wt%, about 18.7
wt%, about 18.8
wt%, about 18.9 wt%, about 19.0 wt%, about 19.1 wt%, about 19.2 wt%, about
19.3 wt%, about
19.4 wt%, about 19.5 wt%, about 19.6 wt%, about 19.7 wt%, about 19.8 wt%,
about 19.9 wt%,
about 20.0 wt%, about 20.1 wt%, about 20.2 wt%, about 20.3 wt%, about 20.4
wt%, about 20.5
wt%, about 20.6 wt%, about 20.7 wt%, about 20.8 wt%, about 20.9 wt%, about
21.0 wt%, about
21.1 wt%, about 21.2 wt%, about 21.3 wt%, about 21.4 wt%, about 21.5 wt%,
about 21.6 wt%,
about 21.7 wt%, about 21.8 wt%, about 21.9 wt%, about 22.0 wt%, about 22.1
wt%, about 22.2
wt%, about 22.3 wt%, about 22.4 wt%, about 22.5 wt%, about 22.6 wt%, about
22.7 wt%, about
22.8 wt%, about 22.9 wt%, about 23.0 wt%, about 23.1 wt%, about 23.2 wt%,
about 23.3 wt%,
about 23.4 wt%, about 23.5 wt%, about 23.6 wt%, about 23.7 wt%, about 23.8
wt%, about 23.9
wt%, about 24.0 wt%, about 24.1 wt%, about 24.2 wt%, about 24.3 wt%, about
24.4 wt%, about
24.5 wt%, about 24.6 wt%, about 24.7 wt%, about 24.8 wt%, about 24.9 wt%,
about 25.0 wt%,
about 25.1 wt%, about 25.2 wt%, about 25.3 wt%, about 25.4 wt%, about 25.5
wt%, about 25.6
wt%, about 25.7 wt%, about 25.8 wt%, about 25.9 wt%, about 26.0 wt%, about
26.1 wt%, about
26.2 wt%, about 26.3 wt%, about 26.4 wt%, about 26.5 wt%, about 26.6 wt%,
about 26.7 wt%,
about 26.8 wt%, about 26.9 wt%, about 27.0 wt%, about 27.1 wt%, about 27.2
wt%, about 27.3
wt%, about 27.4 wt%, about 27.5 wt%, about 27.6 wt%, about 27.7 wt%, about
27.8 wt%, about
27.9 wt%, about 28.0 wt%, about 28.1 wt%, about 28.2 wt%, about 28.3 wt%,
about 28.4 wt%,
about 28.5 wt%, about 28.6 wt%, about 28.7 wt%, about 28.8 wt%, about 28.9
wt%, about 29.0
wt%, about 29.1 wt%, about 29.2 wt%, about 29.3 wt%, about 29.4 wt%, about
29.5 wt%, about
29.6 wt%, about 29.7 wt%, about 29.8 wt%, about 29.9 wt%, about 30.0 wt%,
about 30.1 wt%,
about 30.2 wt%, about 30.3 wt%, about 30.4 wt%, about 30.5 wt%, about 30.6
wt%, about 30.7
wt%, about 30.8 wt%, about 30.9 wt%, about 31.0 wt%, about 31.1 wt%, about
31.2 wt%, about
31.3 wt%, about 31.4 wt%, about 31.5 wt%, about 31.6 wt%, about 31.7 wt%,
about 31.8 wt%,
about 31.9 wt%, about 32.0 wt%, about 32.1 wt%, about 32.2 wt%, about 32.3
wt%, about 32.4
42
Date Recue/Date Received 2023-08-18
wt%, about 32.5 wt%, about 32.6 wt%, about 32.7 wt%, about 32.8 wt%, about
32.9 wt%, about
33.0 wt%, about 33.1 wt%, about 33.2 wt%, about 33.3 wt%, about 33.4 wt%,
about 33.5 wt%,
about 33.6 wt%, about 33.7 wt%, about 33.8 wt%, about 33.9 wt%, about 34.0
wt%, about 34.1
wt%, about 34.2 wt%, about 34.3 wt%, about 34.4 wt%, about 34.5 wt%, about
34.6 wt%, about
34.7 wt%, about 34.8 wt%, about 34.9 wt%, about 35.0 wt%, about 35.1 wt%,
about 35.2 wt%,
about 35.3 wt%, about 35.4 wt%, about 35.5 wt%, about 35.6 wt%, about 35.7
wt%, about 35.8
wt%, about 35.9 wt%, about 36.0 wt%, about 36.1 wt%, about 36.2 wt%, about
36.3 wt%, about
36.4 wt%, about 36.5 wt%, about 36.6 wt%, about 36.7 wt%, about 36.8 wt%,
about 36.9 wt%,
about 37.0 wt%, about 37.1 wt%, about 37.2 wt%, about 37.3 wt%, about 37.4
wt%, about 37.5
wt%, about 37.6 wt%, about 37.7 wt%, about 37.8 wt%, about 37.9 wt%, about
38.0 wt%, about
38.1 wt%, about 38.2 wt%, about 38.3 wt%, about 38.4 wt%, about 38.5 wt%,
about 38.6 wt%,
about 38.7 wt%, about 38.8 wt%, about 38.9 wt%, about 39.0 wt%, about 39.1
wt%, about 39.2
wt%, about 39.3 wt%, about 39.4 wt%, about 39.5 wt%, about 39.6 wt%, about
39.7 wt%, about
39.8 wt%, about 39.9 wt%, about 40.0 wt%, about 40.1 wt%, about 40.2 wt%,
about 40.3 wt%,
about 40.4 wt%, about 40.5 wt%, about 40.6 wt%, about 40.7 wt%, about 40.8
wt%, about 40.9
wt%, about 41.0 wt%, about 41.1 wt%, about 41.2 wt%, about 41.3 wt%, about
41.4 wt%, about
41.5 wt%, about 41.6 wt%, about 41.7 wt%, about 41.8 wt%, about 41.9 wt%,
about 42.0 wt%,
about 42.1 wt%, about 42.2 wt%, about 42.3 wt%, about 42.4 wt%, about 42.5
wt%, about 42.6
wt%, about 42.7 wt%, about 42.8 wt%, about 42.9 wt%, about 43.0 wt%, about
43.1 wt%, about
43.2 wt%, about 43.3 wt%, about 43.4 wt%, about 43.5 wt%, about 43.6 wt%,
about 43.7 wt%,
about 43.8 wt%, about 43.9 wt%, about 44.0 wt%, about 44.1 wt%, about 44.2
wt%, about 44.3
wt%, about 44.4 wt%, about 44.5 wt%, about 44.6 wt%, about 44.7 wt%, about
44.8 wt%, about
44.9 wt%, about 45.0 wt%, about 45.1 wt%, about 45.2 wt%, about 45.3 wt%,
about 45.4 wt%,
about 45.5 wt%, about 45.6 wt%, about 45.7 wt%, about 45.8 wt%, about 45.9
wt%, about 46.0
wt%, about 46.1 wt%, about 46.2 wt%, about 46.3 wt%, about 46.4 wt%, about
46.5 wt%, about
46.6 wt%, about 46.7 wt%, about 46.8 wt%, about 46.9 wt%, about 47.0 wt%,
about 47.1 wt%,
about 47.2 wt%, about 47.3 wt%, about 47.4 wt%, about 47.5 wt%, about 47.6
wt%, about 47.7
wt%, about 47.8 wt%, about 47.9 wt%, about 48.0 wt%, about 48.1 wt%, about
48.2 wt%, about
48.3 wt%, about 48.4 wt%, about 48.5 wt%, about 48.6 wt%, about 48.7 wt%,
about 48.8 wt%,
about 48.9 wt%, about 49.0 wt%, about 49.1 wt%, about 49.2 wt%, about 49.3
wt%, about 49.4
wt%, about 49.5 wt%, about 49.6 wt%, about 49.7 wt%, about 49.8 wt%, about
49.9 wt%, about
50.0 wt%; or any range encompassed by the foregoing values; or any combination
of the
foregoing values.
43
Date Recue/Date Received 2023-08-18
[0095] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising: a therapeutic composition comprising azelaic acid, minoxidil,
finasteride, and
dutasteride; one or more compounding agents; and optionally caffeine and/or
saw palmetto
extract; wherein formulation comprises a therapeutically effective amount of
azelaic acid and
minoxidil; wherein the formulation comprises one or more compounding agent in
a disclosed
amount; and wherein the formulation comprises caffeine present in an amount of
about 0.00010
wt%, about 0.00015 wt%, about 0.00020 wt%, about 0.0025 wt%, about 0.00030
wt%, about
0.00035 wt%, about 0.00040 wt%, about 0.00045 wt%, about 0.00050 wt%, about
0.00055 wt%,
about 0.00060 wt%, about 0.00065 wt%, about 0.00070 wt%, about 0.00075 wt%,
about
0.00080 wt%, about 0.00085 wt%, about 0.00090 wt%, about 0.00095 wt%, about
0.00100 wt%,
about 0.00105 wt%, about 0.00110 wt%, about 0.00115 wt%, about 0.00120 wt%,
about
0.00125 wt%, about 0.00130 wt%, about 0.00135 wt%, about 0.00140 wt%, about
0.00145 wt%,
about 0.00150 wt%, about 0.00155 wt%, about 0.00160 wt%, about 0.00165 wt%,
about
0.00170 wt%, about 0.00175 wt%, about 0.00180 wt%, about 0.00185 wt%, about
0.00190 wt%,
about 0.00195 wt%,about 0.0020 wt%, about 0.0025 wt%, about 0.0030 wt%, about
0.0035
wt%, about 0.0040 wt%, about 0.0045 wt%, about 0.0050 wt%, about 0.0055 wt%,
about 0.0060
wt%, about 0.0065 wt%, about 0.0070 wt%; or any range encompassed by the
foregoing
values; or any combination of the foregoing values.
[0096] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising azelaic acid and minoxidil; one or more compounding agents; and
optionally caffeine
and/or saw palmetto extract; wherein formulation comprises a therapeutically
effective amount
of azelaic acid and minoxidil; wherein the formulation comprises one or more
compounding
agent in a disclosed amount; and wherein the formulation comprises saw
palmetto extract
present in an amount of about 0.10 wt%, about 0.20 wt%, about 0.30 wt%, about
0.40 wt%,
about 0.50 wt%, about 0.60 wt%, about 0.70 wt%, about 0.80 wt%, about 0.90
wt%, about 1.0
wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5
wt%, about 1.6
wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2.0 wt%, about 2.1
wt%, about 2.2
wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7
wt%, about 2.8
wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%, about 3.2 wt%, about 3.3
wt%, about 3.4
wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%, about 3.8 wt%, about 3.9
wt%, about 4.0
wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%, about 4.4 wt%, about 4.5
wt%, about 4.6
wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%, about 5.0 wt%, about 5.1
wt%, about 5.2
44
Date Recue/Date Received 2023-08-18
wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%, about 5.6 wt%, about 5.7
wt%, about 5.8
wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%, about 6.2 wt%, about 6.3
wt%, about 6.4
wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%, about 6.8 wt%, about 6.9
wt%, about 7.0
wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%, about 7.4 wt%, about 7.5
wt%, about 7.6
wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%, about 8.0 wt%, about 8.1
wt%, about 8.2
wt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%, about 8.6 wt%, about 8.7
wt%, about 8.8
wt%, about 8.9 wt%, about 9.0 wt%, about 9.1 wt%, about 9.2 wt%, about 9.3
wt%, about 9.4
wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%, about 9.8 wt%, about 9.9
wt%, about 10.0
wt%, about 10.1 wt%, about 10.2 wt%, about 10.3 wt%, about 10.4 wt%, about
10.5 wt%, about
10.6 wt%, about 10.7 wt%, about 10.8 wt%, about 10.9 wt%, about 11.0 wt%,
about 11.1 wt%,
about 11.2 wt%, about 11.3 wt%, about 11.4 wt%, about 11.5 wt%, about 11.6
wt%, about 11.7
wt%, about 11.8 wt%, about 11.9 wt%, about 12.0 wt%, about 12.1 wt%, about
12.2 wt%, about
12.3 wt%, about 12.4 wt%, about 12.5 wt%, about 12.6 wt%, about 12.7 wt%,
about 12.8 wt%,
about 12.9 wt%, about 13.0 wt%, about 13.1 wt%, about 13.2 wt%, about 13.3
wt%, about 13.4
wt%, about 13.5 wt%, about 13.6 wt%, about 13.7 wt%, about 13.8 wt%, about
13.9 wt%, about
14.0 wt%, about 14.1 wt%, about 14.2 wt%, about 14.3 wt%, about 14.4 wt%,
about 14.5 wt%,
about 14.6 wt%, about 14.7 wt%, about 14.8 wt%, about 14.9 wt%, about 15.0
wt%; or any
range encompassed by the foregoing values; or any combination of the foregoing
values.
[0097] In a further aspect, the disclosed topical formulation the present
disclosure pertains to
topical formulations for treatment of hair loss and/or to increase hair
growth, the formulation
comprising: a therapeutic composition comprising azelaic acid and minoxidil;
one or more
compounding agents; and optionally caffeine and/or saw palmetto extract;
wherein formulation
comprises a therapeutically effective amount of azelaic acid and minoxidil;
wherein the
formulation comprises one or more compounding agent in a disclosed amount;
wherein the
formulation comprises caffeine present in an amount of about 0.00010 wt%,
about 0.00015
wt%, about 0.00020 wt%, about 0.0025 wt%, about 0.00030 wt%, about 0.00035
wt%, about
0.00040 wt%, about 0.00045 wt%, about 0.00050 wt%, about 0.00055 wt%, about
0.00060 wt%,
about 0.00065 wt%, about 0.00070 wt%, about 0.00075 wt%, about 0.00080 wt%,
about
0.00085 wt%, about 0.00090 wt%, about 0.00095 wt%, about 0.00100 wt%, about
0.00105 wt%,
about 0.00110 wt%, about 0.00115 wt%, about 0.00120 wt%, about 0.00125 wt%,
about
0.00130 wt%, about 0.00135 wt%, about 0.00140 wt%, about 0.00145 wt%, about
0.00150 wt%,
about 0.00155 wt%, about 0.00160 wt%, about 0.00165 wt%, about 0.00170 wt%,
about
0.00175 wt%, about 0.00180 wt%, about 0.00185 wt%, about 0.00190 wt%, about
0.00195
wt%,about 0.0020 wt%, about 0.0025 wt%, about 0.0030 wt%, about 0.0035 wt%,
about 0.0040
Date Recue/Date Received 2023-08-18
wt%, about 0.0045 wt%, about 0.0050 wt%, about 0.0055 wt%, about 0.0060 wt%,
about 0.0065
wt%, about 0.0070 wt%; or any range encompassed by the foregoing values; or
any
combination of the foregoing values; and wherein the formulation comprises saw
palmetto
extract present in an amount of about 0.10 wt%, about 0.20 wt%, about 0.30
wt%, about 0.40
wt%, about 0.50 wt%, about 0.60 wt%, about 0.70 wt%, about 0.80 wt%, about
0.90 wt%, about
1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5
wt%, about
1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2.0 wt%, about 2.1
wt%, about
2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7
wt%, about
2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%, about 3.2 wt%, about 3.3
wt%, about
3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%, about 3.8 wt%, about 3.9
wt%, about
4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%, about 4.4 wt%, about 4.5
wt%, about
4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%, about 5.0 wt%, about 5.1
wt%, about
5.2 wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%, about 5.6 wt%, about 5.7
wt%, about
5.8 wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%, about 6.2 wt%, about 6.3
wt%, about
6.4 wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%, about 6.8 wt%, about 6.9
wt%, about
7.0 wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%, about 7.4 wt%, about 7.5
wt%, about
7.6 wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%, about 8.0 wt%, about 8.1
wt%, about
8.2 vvt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%, about 8.6 wt%, about
8.7 wt%, about
8.8 wt%, about 8.9 wt%, about 9.0 wt%, about 9.1 wt%, about 9.2 wt%, about 9.3
wt%, about
9.4 wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%, about 9.8 wt%, about 9.9
wt%, about
10.0 wt%, about 10.1 wt%, about 10.2 wt%, about 10.3 wt%, about 10.4 wt%,
about 10.5 wt%,
about 10.6 wt%, about 10/ wt%, about 10.8 wt%, about 10.9 wt%, about 11.0 wt%,
about 11.1
wt%, about 11.2 wt%, about 11.3 wt%, about 11.4 wt%, about 11.5 wt%, about
11.6 wt%, about
11.7 wt%, about 11.8 wt%, about 11.9 wt%, about 12.0 wt%, about 12.1 wt%,
about 12.2 wt%,
about 12.3 wt%, about 12.4 wt%, about 12.5 wt%, about 12.6 wt%, about 12.7
wt%, about 12.8
wt%, about 12.9 wt%, about 13.0 wt%, about 13.1 wt%, about 13.2 wt%, about
13.3 wt%, about
13.4 wt%, about 13.5 wt%, about 13.6 wt%, about 13.7 wt%, about 13.8 wt%,
about 13.9 wt%,
about 14.0 wt%, about 14.1 wt%, about 14.2 wt%, about 14.3 wt%, about 14.4
wt%, about 14.5
wt%, about 14.6 wt%, about 14.7 wt%, about 14.8 wt%, about 14.9 wt%, about
15.0 wt%; or any
range encompassed by the foregoing values; or any combination of the foregoing
values.
[0098] The topical formulations of the present disclosures may be formulated
into a variety of
topically administrable formulations, such as solutions, suspensions, lotions,
gels, pastes,
medicated sticks, balms, creams, ointments, foams or transdermal patches.
46
Date Recue/Date Received 2023-08-18
[0099] Topical formulations in the form of a topical solution tend to be of
low viscosity, and often
use water or alcohol as the base. They can be formed by dissolving powder in
water, alcohol
and sometimes oil. If alcohol is used as the base, it can cause drying of the
skin. Lotions are
similar to solutions but are thicker and tend to be more emollient in nature
than solutions.
Lotions usually have an oil mixed with water and, more often than not, have
less alcohol than
solutions.
[0100] A topical formulation in the form of a topical cream has an emulsion of
oil and water in
approximately equal proportions. It penetrates the stratum corneum outer layer
of the skin well.
Cream is thicker than lotion and maintains its shape when removed from its
container. It tends
to be moderate in moisturizing tendency.
[0101] A topical formulation in the form of a topical ointment is a
homogeneous, semi-solid
preparation, most commonly a greasy, thick oil (e.g., oil 80%-water 20%) with
a high viscosity
that is intended for external application to the skin or mucus membranes.
Ointments are
formulated using hydrophobic, hydrophilic or water-emulsifying bases to
provide preparations
that are immiscible, miscible or emulsifiable with skin secretions. Ointments
can also be derived
from hydrocarbon (fatty), absorption, water-removable or water-soluble bases.
Gels are often a
semisolid emulsion, such as cellulose, in an alcohol or acetone base.
[0102] A topical formulation in the form of a transdermal patch can be a very
precise time
release method of delivering a drug. The release of the active component from
a transdermal
patch may be controlled by diffusion through the adhesive which covers the
whole patch, by
diffusion through a membrane which may only have adhesive on the patch rim or
controlled by
release from a polymer matrix.
[0103] A suitable gel base for gel-cream emulsions is one that has one or more
of the following
characteristics: noncomedogenic, hypoallergenic, non-irritating, odor-free,
comprises natural
emulsifiers, non-ionic emulsion system that is compatible with cationic and
anionic substances,
and that is stable over a broad pH range, such as about pH 3.5 to pH12. An
exemplary, but non-
limiting example of a suitable gel base for gel-cream emulsions is the
commercially available
Versabase Gel from Professional Compounding Pharmacies of America (PCCA; 9901
South
Wilcrest Dr., Houston, Texas), and reportedly contains ammonium
acryloyldimethyltaurateiVP
Copolymer, aloe vera, edetate disodium, allantoin, methylchloroisothiazolinone
and
methylisothiazolinone. Versabase Gel is designed as an inert base for
compounding
formulations for topical preparations. In a further aspect, a suitable gel
base for gel-cream
emulsions is chosen from the group consisting of VersaBase, LIPODERM,
PENTRAVAN,
47
Date Recue/Date Received 2023-08-18
Pluronic Lecithin Organogel (PLO), and mixtures thereof.
[0104] In some aspects, the gel base for gel-cream emulsions comprises water,
ammonium
acryloyldimethyltaurate copolymer, aloe barbadensis leaf juice powder,
allatoin, disodium
EDTA, methylchloroisothiazoli none and methylisothiazoli
none. The ammonium
acryloyldimethyltaurate/VP Copolymer may act as a gelling agent for the
aqueous solution to
allow for topical application without dripping or drying out. The aloe vera
may enhance skin
penetration of the active botanical constituents allowing for transdermal
uptake. The allantoin
may act as a keratolytic agent to improve moisture binding capacity of the
epidermis to also
improve drug penetration into the skin.
[0105] In further aspects, gel base for gel-cream emulsions with these
activities, i.e.,
transdermal absorption and surface adhesion, may be used in a disclosed
topical formulation.
For example, other suitable gel base for gel-cream emulsions include: LIPODERM
(Professional Compounding Centers of America, Inc., Houston, Tex.), PENTRAVAN)
(Fargon,
Inc., St. Paul, Minn.), and Pluronic Lecithin Organogel. LIPODERM reportedly
comprises
ethoxydiglycol, water, glycerin, C12-C15 alkyl benzoate, glyceryl stearate,
dimethicone, cetearyl
alcohol, cetearyl glucoside, polyacrylamide, cetyl alcohol, magnesium aluminum
silicate,
xanthan gum, aloe vera, tocopheryl acetate, bitter almond kernel oil, grape
seed extract, wheat
germ oil, vitamin-A palmitate, vitamin-C palmitate, ProLipo mutli-emulsion
liposomic system,
tetrasodium EDTA, phenoxyethanol and sodium hydroxymethyl glycinate.
[0106] In a further aspect, rather than using commercially available bases
such as these,
ingredients similar to those found in these bases may be used to form new
bases that can be
used in the therapeutic compositions herein. For example, other fatty acids,
fatty acid esters,
alkoxylated fatty acids, alkoxylated fatty acid esters, monoglycerides,
diglycerides, triglycerides,
sorbitan fatty acid esters, fatty alcohols, oils, lipids, gums, polymers, and
the like, may be
compounded with the therapeutic agents discussed to produce therapeutic
compositions within
the scope of the present disclosure.
[0107] In various aspects, a disclosed topical formulation comprises a
silicone base. For
example, a suitable commercially available silicone base is a topical
anhydrous silicone base
such as PracaSil PlusTM, manufactured by PCCA, and Scar Care Base Enhanced,
manufactured 'by Letco Medical (1316 Commerce Drive NW, Decatur, Alabama
35601).
[0108] In a further aspect, a suitable silicone base can comprise dimethicone,
dimethiconol,
cyclopentasiloxane, cetyl dimethicone, phenyl trimethicone, low hexyl
dimethicone, or
48
Date Recue/Date Received 2023-08-18
combinations thereof. In a still further aspect, a suitable silicone base can
comprise
cyclopentasiloxane, polysilicone-11, C30-45 alkyl cetearyl dimethicone
crosspolymer,
dimethiconol, phenyl trimethicone, PEG PPG dimethicone, or combinations
thereof. The silicone
base can further comprise non-silicone components such as Carapa guaianensis
seed oil,
macadamia nut oil, laureth-4, PEG 30 dipolyhydroxystearate, or combinations
thereof.
[0109] In a further aspect, a silicone base can comprise ingredients such as
cyclopentasiloxane; polysilicone-11; dimethicone; and/or C30-45 alkyl cetearyl
dimethicone
crosspolymer. Briefly, cyclopentasiloxane is a type of silicone, and may have
the ability to
lubricate, and may be waterproof and provide shine. Cyclopentasiloxane may
have a very sticky
consistency, and may be volatile and/or used in combination with dimethicone.
The
cyclopentasiloxane may be combined with polysilicone-11, which may be a
synthetic
crosslinked siloxane that functions as a film-forming agent and polymer,
and/or C30-45 alkyl
cetearyl dimethicone crosspolymer, which may be a coploymer of C30-45 alkyl
cetearyl
dimthicone crosslinked with vinyl cyclohexene oxide, or another copolymer.
[0110] In another aspect, the silicone base may comprise silicone components,
such as those
disclosed by U.S. Pat. No. 6,827,929; U.S. Pat. No. 6,337,076; U.S.
Publication No.
2011/0046532; U.S. Publication No. 2010/0322875; U.S. Publication No.
2009/0143333; and/or
U.S. Publication No. 2006/0029672. Silicone bases having additional, fewer, or
alternate
ingredients may be used.
[0111] Without wishing to be bound by a particular theory, it is believed that
the silicone base
may facilitate the permeation of the therapeutic composition in the silicone
base through the
skin of a patient when the silicone base is topically applied. The silicone
may be a polymer,
such as plastic or rubber, containing silicon. Silicone variants or variations
of silicone that may
be used with the silicone base may include silicone or silicone derivatives
that are in gel, fluid,
powder, or other forms. The silicone or silicone variants may include silicon,
silicon oxide, silicon
dioxide, silica, medical grade silicone, professional grade silicone, or other
forms of silicone
and/or silicon.
[0112] In various aspects, the disclosed topical formulations can comprise a
fatty acid. Any fatty
acid, or combination of fatty acids, may be blended with the disclosed
therapeutic agents herein
to produce a disclosed topical formulation. For example, any C6-C24 fatty acid
may be used in
the pharmaceutical formulas of the present disclosure. Fatty acids for use
herein also include
C6-C24 fatty acids having any degree of unsaturation in the carbon chain.
Fatty acids for use
herein may be from natural oil and fat sources such as tallow, lard, coconut
oil, palm oil, peanut
49
Date Recue/Date Received 2023-08-18
oil, rice bran oil, olive oil, cottonseed oil, wheat germ oil, soy bean oil,
corn oil, sunflower oil, and
safflower oil, amongst others. Natural oils may supply a distribution of fatty
acid chain lengths.
For therapeutic compositions within the scope of the present disclosure, any
combination of free
fatty acid, natural oils, hydrogenated oils, partially hydrogenated oils,
vegetable and animal fats,
monoglycerides, diglycerides and triglycerides may be used, and may be
combined with any
other emulsifiers, emollients, carriers, solubilizers, solvents, and the like,
as desired.
[0113] In certain aspects, the compositions comprise a thickening agent. The
thickening agent
may be monomeric, oligomeric or polymeric in its nature, or any combination of
monomeric,
oligomeric or polymeric thickening agents thereof. Exemplary monomeric
thickening agents
include alcohols and esters, for example, fatty alcohols, esters of fatty
alcohols, and fatty acid
esters, any of which may be isolated from natural sources or synthetically
derived. Fatty
alcohols are exemplified by any C12-C24straight chain or branched alcohol, or
any combination of
two or more C,2-C24straight chain or branched alcohols. By way of example, a
fatty alcohol,
preferably comprising cetyl alcohol or stearyl alcohol or combination thereof,
may be present in
the composition in the range of from about 0.05% to about 2% by weight,
preferably from about
0.1% to about 1% by weight, more preferably from about 0.1% to about 0.5% by
weight, with
from about 0.1 to about 0.3% by weight being even more preferred. These fatty
alcohols may be
used alone or in conjunction with glyceryl esters of fatty acids or
ethoxylated fatty acid esters,
such as polyethylene glycol esters of fatty acids, or any combination thereof.
Thickening agents
may also be selected based on their hydrophilic-lipophilic balance. Typically,
such thickening
agents have emulsification or composition stiffening properties and will
usually have and HLB
value of from about 12 to about 16. These agents may assist in the formation
of oil in water
emulsions and provide certain desired viscosity properties to the final
compositions. In some
aspects, the thickening agent comprises glyceryl esters, preferably glyceryl
esters of fatty acids,
such as glyceryl stearate. Additional examples of alcohol ethoxylates may be
found in Kirk-
Othmer Encyclopedia of Chemical Technology, ad Edition, Volume 22, pages 364
and 365.
Numerous examples of other glyceryl esters of fatty acids may be found in Kirk-
Othmer
Encyclopedia of Chemical Technology, 3rd Edition, Volume 22, pages 367 and
368. These esters
may be used alone or in conjunction with ethoxylated fatty acid esters, such
as polyethylene
glycol esters of fatty acids. For example, in some aspects, a mixture of
glyceryl stearate and
PEG-100 stearate is employed as a thickening agent in the composition. Various
combinations
(ratios) of these two agents may be used by one of ordinary skill in the art
to appropriately
thicken or stiffen the composition to assist in its localization once applied
to tissue. In certain
preferred aspects, about 2 wt. parts of glyceryl stearate per wt. part of PEG-
100 stearate
Date Recue/Date Received 2023-08-18
provides satisfactory results when used at a combined weight level of from
about 2% to about
12% by weight of the composition; preferably from about 3% to about 11% by
weight; more
preferably from about 4% to about 10% by weight; with from about 5% to about
10% by weight
being even more preferred. Alternatively, polyethylene glycol esters of fatty
acids may be used
as thickening agents. In other alternative aspects, the thickening agent
comprises silica.
Additional organic or inorganic thickening agents are known in the art.
[0114] In still other aspects, the thickening agents comprise an anionic or
non-ionic polymer or
copolymer. In addition to their usefulness as thickeners, these anionic or non-
ionic polymers or
copolymers may also provide better substantivity. These features allow the
compositions to be
retained on the tissue even while being exposed to bodily fluids or sweat and
the like, and yet,
preferably, still be reasonably easily removed when desired with mild cleaning
agents such as
soap and water. Generally speaking, the anionic or non-ionic polymers or
copolymers comprise
hydrophilic and hydrophobic moieties. When more substantivity in the
compositions of the
present disclosure is desired, an anionic or non-ionic polymer or copolymer
should be selected
based on higher levels of hydrophobic moieties. When more fluidity is desired,
the level of
hydrophilic moieties should be increased relative to the hydrophobic moieties.
Non-limiting
examples generally include anionic or non-ionic acrylate copolymers or
carbomers.
[0115] In some aspects preferred copolymer thickening agents comprise
copolymers of
ammonium acryloyldimethyltaurate and vinylpyrrolidone monomers, or copolymers
of C10-
C30alkyl acrylate with monomers of acrylic acid or methacrylic acid or any
combination thereof.
Examples of some commercially available polymeric thickening agents include
VersaBase
Gel (PCCA, 9901 South Wi'crest Drive Houston, Tex. 77099); Carbomer Gel
(Letco Medical,
1316 Commerce Drive, NW Decatur, Ala. 35601); and Adaptaderm Gel (Freedom
Pharmaceuticals, 801 W. New Orleans St., Broken Arrow, Okla. 74011).
[0116] In a further aspect, anionic acrylate copolymers include copolymers of
acrylic acid,
acrylamide, sodium acrylate and sodium acryloyldimethyltaurate monomers, such
as, for
example, Polyacrylate-13 and the like. While such polymers may be used as
thickening agents
alone, they may also be used in combination other known thickening agents
including
polyisobutene and/or polysorbitan polyethoxylates and their fatty acid esters,
such as for
example, Polysorbate 20. One such advantageous combination of Polyacrylate-13,
Polyisobutene, and Polysorbate 20, known under the trade name SEPIPLUSTm 400,
is provided
by Societe d'Exploitation de Produits Pour les Industries Chimiques, Paris
France. In other
alternative aspects, thickening agents comprise a non-ionic copolymer, such as
for example, a
51
Date Recue/Date Received 2023-08-18
poloxamer. Poloxamers are nonionic triblock copolymers composed of a central
hydrophobic
chain of polyoxypropylene (poly(propylene oxide)) flanked by two hydrophilic
chains of
polyoxyethylene (poly(ethylene oxide)) and have the general structure shown
below wherein
a=2-130 and b=15-67:
0,14Nwo") 0'61
[0117] Because the lengths of the polymer blocks can be customized, many
different
poloxamers exist that have slightly different properties, which are well
understood to those of
ordinary skill in the art. Once armed with the disclosures herein, any of a
number of poloxamers
may be chosen for use dependent at least in part on the properties desired in
the final product.
Because of their amphiphilic structure, the polymers have surfactant
properties that make them
useful in industrial applications. Among other things, they can be used to
increase the water
solubility of hydrophobic, oily substances or otherwise increase the
miscibility of two substances
with different hydrophobicities. Typically, the poloxamers of the present
disclosure have the
structure of Formula I wherein each a is independently in the range of from
about 80 to about
120, preferably from about 90 to about 110, and b is in the range of from
about 50 to about 80,
preferably from about 55 to about 70. In other alternative aspects, the
typical the poloxamers
have an approximate molecular mass of the poly(oxypropylene) core of 3500 to
about 4500
g/mol and about 65 to about 75% of poly(oxyethylene) content by weight of the
poloxamer. An
exemplary poloxamer of this class for use in the compositions of the present
disclosure is
Poloxamer 407. Poloxamer 407 is a triblock copolymer which includes a central
hydrophobic
block of polypropylene glycol flanked by two hydrophilic blocks of
polyethylene glycol. The
approximate lengths of the two PEG blocks is 101 repeat units while the
approximate length of
the propylene glycol block is 56 repeat units. This particular compound is
also known by the
BASF trade name Pluronic F127 or by the Croda trade name Synperonic PE/F 127.
In addition
to viscosity modification properties, poloxamers, including Poloxamer 407, are
known to
incorporate into cellular membranes forming a biocompatible film. Without
being held to theories
of action, it is believed that formation of such a biocompatible film may
allow the PVP/iodine
element of the present disclosure to remain in contact with skin tissue such
as that located on
the scalp for extended periods of time
[0118] Typically, anionic or non-ionic polymer or copolymer levels in
antimicrobial compositions
52
Date Recue/Date Received 2023-08-18
of the present disclosure are in the range of from about 0.1 to about 6% by
weight of the
composition, preferably from about 0.1 to about 5.5% by weight of the
composition, still more
preferably from about 2 to about 3% by weight of the composition. In
combination-type polymer
or co-polymer thickening agents, the relative ratio of the two or more
components is not critical
insofar as it does not interfere with the efficacy of the antimicrobial
agent(s) and/or the
substantivity on skin of the final composition. By way of guidance, a relative
wt. ratio of
Polyacrylate-13/Polyisobutene/Polysorbate 20 of from about 15:6:1 to about
10:5:1. In other
aspects, the relative wt. ratio of Polyacrylate-13 to Polyisobutene in the
formulation is from
about 3:1 to about 1:3, and all combinations and subcombinations thereof. In
certain other
aspects, the relative wt. ratio of Polyacrylate-13 to Polysorbate 20 in the
formulation is from
about 5:1 to about 20:1, and all combinations and subcombinations thereof.
[0119] In yet other aspects, the thickening agents comprise a modified
cellulose derivative such
as, for example, non-ionic soluble cellulose ethers. Hydroxyethyl cellulose is
an exemplary
compound in this family, and is soluble in both hot and cold water.
Hydroxyethyl cellulose has
good water retention and film formation. Owing to good thickening, suspending,
dispersing,
emulsifying, film-forming, water-protecting and protective colloid properties,
hydroxyethyl
cellulose has been shown to be useful in coatings, medicines, foods, and other
fields. Modified
cellulose derivatives such as, for example, non-ionic soluble cellulose ethers
may be considered
polymeric as well based on their backbone of repeating monosaccharides.
[0120] While such modified cellulose derivatives may be used as thickening
agents alone, they
may also be used in combination other known thickening agents, such as any
families or
individual thickening agents noted herein. By way of example, non-ionic
soluble cellulose
ethers, preferably comprising hydroxyethyl cellulose may be present in the
composition in the
range of from about 0.05% to about 5% by weight, preferably from about 0.1% to
about 3% by
weight, more preferably from about 0.1% to about 0.5% by weight, with from
about 0.1 to about
0.3% by weight being even more preferred.
[0121] A suitable liquid vehicle for the antiseptic compositions of the
present disclosure
comprises water, to which acetone or an alcohol, particularly a (C1-C4)
alcohol (i.e., a lower
alcohol) such as ethanol, 2-propanol, and n-propanol, and mixtures thereof may
be added. The
use of alcohols in combination with water may enhance initial antimicrobial
activity on tissue, or
alternatively allow for reductions in surfactant levels. Preferably, the water
is purified by any
suitable means; more preferably the water or other vehicle is USP grade,
including injectable-
grade water, i.e., USP grade "water for injection.
53
Date Recue/Date Received 2023-08-18
[0122] Aqueous formulations (of the "non-lower alcohol" type) are typically
preferred due at
least in part to their gentleness to skin tissue.
[0123] In formulating the disclosed topical formulations, it is contemplated
that the formulations
may further comprise ingredients which, while not having the activity of the
above-named
ingredients, will aid in the formulation and use of the composition as a
whole. Examples of such
ingredients are well-known to those of ordinary skill in the art of producing
formulations for
biological purposes. Examples of these ingredients include such substances as
binders,
emollients, humectants, preservatives (such as methyl paraben), lubricants,
colorants,
perfumes, and the like, such as those described in U.S. Pat. No. 5,951,993
(Scholz et al.),
fragrances, colorants, tackifiers, plasticizers, and the like. Accordingly,
when the surface
contemplated is skin, the composition of this disclosure may contain
ingredients which are
added to known lotions or medicaments, which are physiologically acceptable to
skin and which
do not contain ingredients which will reverse or retard the action of the
irritant-inactivating agent.
Surfactants may also be added to disperse the organic components or improve
their solubility,
inter alia, in the aqueous vehicle. In some aspects, the compositions of the
disclosure further
comprise glycerin alone or in combination with allantoin. In certain
alternative aspects, the
compositions of the disclosure further comprise a short chain (C1-C4) alcohol,
a benzyl alcohol,
an ethanol amine such as triethanol amine, or an emollient such as aloe, or
any combination
thereof.
[0124] In some aspects, the compositions further comprise a surfactant. When
the
compositions include a surfactant, the surfactant may be anionic, cationic,
amphoteric or non-
ionic, or combination thereof. Alternatively, the surfactant is anionic or
nonionic. In other aspects
that include, a surfactant, it is nonionic. Surfactants may play any number of
roles in the
preparation and/or application of the compositions of the present disclosure,
including, for
example, improving the solubility or uniformity of dispersion for an iodophor
in the aqueous
composition. Alternatively or in combination, it may act to assist in reducing
surface tension
during application to mucosal tissue or skin tissue and/or facilitate drying
of the composition on
a tissue surface. They may also act to thicken the composition. Numerous
examples of this
class of molecules are known in the art. In certain aspects, the surfactant
acts to assist in
emulsifying the more hydrophobic components in the aqueous composition.
Preferably, the
hydrophilic-lipophilic balance, as calculated by Griffin's method, is in the
range of from about 8
to about 15, more preferably from about 8 to about 13, still more preferably
from about 9 to
about 12. Exemplary surfactants of this type include both anionic and non-
ionic surfactants,
54
Date Recue/Date Received 2023-08-18
preferably nonionics. Specific non-limiting examples of non-ionic surfactants
of this type are
fatty alcohol ethoxylates such as laureth 4. By way of example, the
surfactant, preferably
laureth-4, is present in the composition in the range of from about 2% to
about 8% by weight,
preferably from about 3% to about 7% by weight, more preferably from about 3%
to about 6%
by weight, with from about 3% to about 5% by weight of the composition being
even more
preferred. In alternative aspects, the surfactant, preferably laureth-4, is
present in the
composition in the range of from about 1% to about 10% by weight, preferably
from about 1% to
about 7% by weight, more preferably from about 1% to about 6% by weight.
Alternately
preferred compositions contain non-ionic surfactants at levels in a range of
from about 0.5% to
about 7% by weight, preferably from about 1% to about 6% by weight, more
preferably from
about 1.5% to about 4% by weight, with from about 2% to about 3% by weight of
the
composition being even more preferred. Additional examples may be found in
Kirk Othmer
Encyclopedia of Chemical Technology, 3rd Edition, Volume 22, pages 364 and
365.
[0125] In yet other aspects, the compositions further comprise an emollient or
moisturizer.
Moisturizers or emollients are mixtures of chemical compounds specially
designed to make the
external layers of the skin (epidermis) softer and more pliable. They increase
the skin's
hydration (water content) by reducing evaporation. Naturally occurring skin
lipids and sterols, as
well as artificial or natural oils, humectants, emollients, lubricants, etc.,
may be part of the
composition of commercial skin moisturizers. They usually are available as
commercial products
for cosmetic and therapeutic uses. Emollients can include, for example, fatty
alcohols such as
C,,to Cõfafty alcohols, naturally occurring oils such as jojoba oils or
products derived from such
oils and esters. In some aspects, the moisturizers also assist in viscosity
building or modifying.
For example, International Flora Technologies, Ltd. Of Chandler, Ariz.
provides certain ester
products, for example, Floraesters 20, Floraesters 30, and Floraesters 60,
based
on Simmondsia chenensis, that have this dual property capability. By way of
example, jojoba
esters, such as Floraesters 20, Floraesters K-20W, Floraesters 30, and
Floraesters 60, may be
present in the compositions of the present disclosure in the range of from
about 1% to about 8%
by weight, preferably from about 2% to about 7% by weight, more preferably
from about 2% to
about 6% by weight. Alternatively preferred ranges for any of the Floraester
products in
compositions of the present disclosure range from about 0.1% to about 6% by
weight,
preferably from about 0.3% to about 6% by weight, more preferably from about
0.5% to about
6% by weight, still more preferably from about 0.5% to about 4% by weight, yet
more preferably
from about 0.5% to about 2% by weight. Other exemplary esters of fatty acids
and fatty
alcohols, saturated and/or unsaturated, from natural or synthetic sources, may
be capable of
Date Recue/Date Received 2023-08-18
providing one or both of these desirable properties.
[0126] Other exemplary emollients include but are not limited to Procetyl 10
PPG-10 cetyl ether,
Procetyl 50 PPG-50 cetyl ether, Promyristyl PM-3 PPG-3Myristyl ether, PPG-3
benzyl ether
myristate (Crodamol STS of Croda), PEG 20 Almond Glycerides, Probutyl DB-10,
Glucam P20,
Glucam E-10, Glucam P-10, Glucam E-20, Glucam P-20 distearate, glycerin,
propylene glycol,
cetyl acetate and acetylated lanolin alcohol (Acetulan), and hydroxylated milk
glycerides.
[0127] In some other aspects, the compositions further comprise glycerin, a
glycerin ether
compound, an ethoxylated glycerin compound, or a combination thereof. In
aspects where the
compositions further comprise glycerin, a glycerin ether compound, an
ethoxylated glycerin
compound, or a combination thereof, the compound or combination it is
typically present as a
thickening agent.
[0128] In some aspects, the carriers and vehicles include, but are not limited
to, micro or
nanocapsules, nanoemulsions/submicron emulsions/miniemulsions, solid lipid
nanoparticles,
multiple emulsions, microemulsions. Vesicular carriers include, but are not
limited to, liposomes,
niosomes, transfersomes, ethosomes, and aquasomes. Chemical penetration
enhancers
include, but are not limited to, sulfoxides and similar chemicals, azone,
pyrrolidones, fatty acids,
essential oils terpenes and terpenoids, oxazolidinones, ureas, water,
alcohols, fatty alcohols,
and glycerols, and surfactants, see, for example, Mathur, V. et al., Physical
and chemical
penetration enhancers in transdermal drug delivery system, Asian J. Pharm.,
4:173-83 (2010)
and Escobar-Chavez, J. J. et al in Pharmacology edited by Luca Gallelli (2012)
and Escobar-
Chavez, J. J. et al. in Pharmacology edited by Luca Gallelli (2012).
[0129] In some aspects the topical formulation comprises chemical penetration
enhancers.
Chemical penetration enhancers include, but are not limited to solvents,
surfactants, and
chemicals. Examples of solvents include, but are not limited to, water,
alcohols such as
methanol and ethanol, alkyl methyl sulfoxide, dimethyl sulfoxide, alkyl
homologs of methyl
sulfoxide such as dimethyl acetamide, and dimethylformamide; pyrrolidones such
as 2-
pyrrolidone, N-methyl, and 2-pyrrolidone; laurocapran (Azone), propylene
glycol, glycerol,
silicone fluids and isopropyl palmitate. Examples of surfactants include
anionic surfactants
including, but not limited to, dioctyl sulphosuccinate, sodium lauryl sulfate
and decodecylmethyl
sulphoxide; cationic surfactants; and nonionic surfactants such as Pluronic
F127 and Pluronic
F68. Other chemical penetration enhancers include bile salts such as sodium
taurocholate,
sodium deoxycholate and sodium tauroglycocholate; binary systems such as
propylene
glycol/oleic acid and 1,4-butanediol/linoleic acid; and chemicals such as N,N-
diethyl-m-
56
Date Recue/Date Received 2023-08-18
toluamide and calcium thioglycolate.
[0130] In another aspect the topical formulation comprises chemical
penetration enhancers
including, but not limited to N-methyl-2-pyrolidone, glycols such as
diethylene glycol, propylene
glycol and tetraethylene glycol, fatty acids including, but not limited to,
lauric, myristic and
capric, nonionic surfactants including, but not limited to, polyoxyethylene-2-
oley1 ether and
polyoxyethylene-2-stearyl ether. In another aspect essential oils of
eucalyptus, chenopodium
and ylang-ylang are used. In one aspect L-menthol, terpenes, oxazolidinones,
and ureas are
used as chemical penetration enhancers see, for example, Pathan, I. B. et al.,
Tropical J.
Pharm. Res., 8(2):173-179 (2009).
[0131] In other aspects the topical formulations comprise common topical
ingredients that
include, but are not limited to, vehicles such as hydrophobic vehicles, water-
miscible vehicle co-
solvents, structural matrix formers; suspending, jelling, or viscosity
inducing agents, water-in-oil
emulsifiers, preservatives, and chelating agents.
[0132] In some aspects, hydrophobic vehicles include hydrocarbons such as
liquid petrolatum
(mineral oil, liquid paraffin, paraffin oil), white petrolatum (petroleum
jelly, Vaseline), yellow
petrolatum (petroleum jelly), and squalane (perhydrosqualene, spinacane);
silicones such as
liquid polydimethylsiloxanes (dimethicone, silastic, medical grade silicone
oil); alcohols such as
lauryl alcohols (1-dodecanol, dodecyl alcohols), myristyl alcohols
(tetradecanol, tetradecyl
alcohols) cetyl alcohols (hexadecanol, ethal, palmityl alcohols), stearyl
alcohols (stenol,
cetosteryl alcohols) and oleyl alcohols (ocenol); sterols and sterol esters,
including, but not
limited to, lanolin (hydrous wool fat, lanum), anhydrous lanolin (wool fat,
anhydrous lanum,
agnin), and semi synthetic lanolin's; carboxylic acids such as lauric acid,
myristic acid, palmitic
acid, stearic acid and oleic acid; esters and polyesters including, but not
limited to, cholesterol
esters (stearate), ethylene glycol monoesters, propylene glycol monoesters,
glyceryl
monoesters, glyceryl monostearate, sorbitol monoesters, sorbitain monoesters,
sorbitol diesters,
sorbitan polyesters (spans, arlacels), glyceryl tristearate, lard, almond oil,
corn oil, castor oil,
cottonseed oil, olive oil, soybean oil, hydrogenated oils, sulfated oils,
isopropyl myristate, and
isopropyl palmitate; ethers and polyethers such as polyethylene-polypropylene
glycols
(pluronics).
[0133] In another aspect, water-miscible vehicle co-solvents include polyols
and polyglycols
such as propylene glycol (1,2-propanediol), glycerin (glycerol), liquid
polyethylene glycol, solid
polyethylene glycol (hard macrogol, carbowax) and 1,2-phenols-hexanetriol,
sorbitol solution
70%; esters and polyesters such as polyoxyethylene sorbitain monoesters
(stearate-tweens)
57
Date Recue/Date Received 2023-08-18
and polyoxy ethylene sorbitan polyesters (tweens); ethers and polyethers,
including but not
limited to, polyethylene glycol monocetyl ether (cetomacrogol 1000) and
polyethylene-
polypropylene glycols (pluronics).
[0134] In other aspects, structural matrix formers include but are not limited
to hydrocarbons,
silicones, polyols and polyglycols, alcohols, sterols and sterol esters,
carboxylic acids, esters
and polyesters. Examples of hydrocarbons include, but are not limited to,
white petrolatum
(petroleum jelly, Vaseline), yellow petrolatum (petroleum jelly), paraffin
(paraffin wax, hard
paraffin), microcrystalline wax and ceresin (mineral wax, purified ozokerite).
Examples of
silicones include, but are not limited to fumed silica (cab-O-sil), bentonite
(colloidal aluminum
silicate) and veegum (colloidal magnesium aluminum silicate). Examples of
polyols and
polyglycols include, but are not limited to solid polyethylene glycol (hard
macrogol, carbowax).
Examples of alcohols include, but are not limited to, cetyl alcohols
(hexadecanol, ethal, palmityl
alcohols) and stearyl alcohols (stenol, cetosteryl alcohols). Examples of
sterols and sterol esters
include, but are not limited to, cholesterol (cholesterin), lanolin (hydrous
wool fat, lanum),
anhydrous lanolin (wool fat, anhydrous lanum, and agnin), and semi-synthetic
lanolin's.
Examples of carboxylic acids include, but are not limited to, lauric acid,
myristic acid, palmitic
acid, stearic acid, and oleic acid. Examples of esters and polyesters include,
but are not limited
to, bees wax, white bees wax (bleached bees wax), carnauba wax, myricin,
cholesterol esters
(stearate), polyoxyethylene sorbitain, monoesters (stearate-tweens), lard, and
hydrogenated
oils.
[0135] In another aspect suspending, jelling or viscosity inducing agents
include silicones,
polycarboxylates, polysulfates, polysaccharides and other compounds. Silicones
include, but
are not limited to, uhmed silica (cab-O-sil), bentonite (colloidal aluminum
silicate) and veegum
(colloidal magnesium aluminum silicate). Polycarboxylates, polysulfates and
polysaccharides
include, but are not limited to, agar, alginates, carrageen, acacia,
tragacanth, methylcellulose,
carboxy methylcellulose, hydroxy ethyl cellulose, carboxy vinyl polymer,
gelatin, pectin, xanthan,
and polyacrylic acid. Other compounds include, but are not limited to,
ethanolamine and
triethanolamine.
[0136] In some aspects, water-in-oil (w/o) emulsifiers include but are not
limited to, sterols and
sterol esters, carboxylic acids, ether and polyethers. Sterols and sterol
esters include, but are
not limited to, cholesterol (cholesterin), lanolin (hydrous wool fat, lanum),
anhydrous lanolin
(wool fat, anhydrous lanum, agnin), and semi-synthetic lanolin's. Carboxylic
acids include, but
are not limited to, the Na, K.' and ethanolamine salts of lauric acid,
myristic acid, palmitic acid,
58
Date Recue/Date Received 2023-08-18
stearic acid, and oleic acid. Ethers and polyethers include, but are not
limited to, polyethylene-
polypropylene glycols (pluronics).
[0137] In another aspect, oil-in-water (o/w) emulsifiers include, but are not
limited to, esters and
polyesters, ethers and polyethers and other miscellaneous reagents. Esters and
polyesters,
include, but are not limited to, polyoxyethylene sorbitain monoesters
(stearate-tweens), polyoxy
ethylene esters (stearate-polyethylene glycol monoesters, Myrj), and polyoxy
ethylene sorbitan
polyesters (tweens). Ethers and polyethers, but are not limited to,
polyethylene glycol monocetyl
ether (cetomacrogol 1000) and polyethylene-polypropylene glycols (pluronics).
Other
miscellaneous reagents, but are not limited to, sodium lauryl sulfate, Borax
(sodium borate),
ethanolamine and triethanolamine.
[0138] In one aspect, chelating agents include but are not limited to, citric
acid and edetic acid.
The chelating agents can be combined with buffers produced from reagents such
as phosphoric
acid, NaH2PO4, glycine, acetic acid, triethanolamine and boric acid. In
another aspect, chelating
agents can be combined with humectants including, but not limited to,
glycerin, propylene
glycol, glyceryl triacetate, sorbitol, xylitol, maltitol, polydextrose,
quillaia, lactic acid, urea, and
lithium chloride.
[0139] In one aspect, ointments comprise therapeutic composition in ointment
bases. Ointment
bases are typically classified by the USP into four general groups (a)
hydrocarbon bases
including but not limited to, petrolatum, USP; white petrolatum, USP; yellow
petrolatum, USP;
white petrolatum, USP; (b) absorption bases that include water-in-oil
emulsions (c) water-
removable bases that include hydrophilic ointment, USP; and (d) water-soluble
bases such as
polyethylene glycol ointment, NF.
[0140] In another aspect, creams comprise therapeutic composition dissolved or
suspended in
water removable or emollient bases. Creams are classified as water-in-oil or
oil-in-water. There
are several types of creams including but not limited to cleaning and cold
cream or lotion,
vanishing and foundation cream, night and massage cream, hand and body cream,
all purpose
cream, and moisturizing cream. Examples of cream bases include (a) cream base,
w/o (rose
water ointment) oleaginous phase including but not limited to, spermaceti,
white wax, almond
oil, sodium borate and an aqueous phase including but not limited to, sodium
borate, stronger
rose water, NF, and water (b) cream base o/w including an oleaginous phase
including but not
limited to, stearyl alcohol, beeswax and sorbitan monooleate, and an aqueous
phase including
but not limited to, sorbitol solution, polysorbate 80, methyl paraben, and
water (c) cream base,
01w (vanishing cream) including an oleaginous phase including, but not limited
to, stearic acid,
59
Date Recue/Date Received 2023-08-18
stearyl alcohol, cetyl alcohol and an aqueous phase including but not limited
to, glycerin, methyl
paraben, propyl paraben, potassium hydroxide, and water.
[0141] In another aspect, a disclosed topical formulation can be formulated as
a paste or gel.
Examples of gelling agents include, but are not limited to, synthetic
macromolecules such as
Carbomer 934 and cellulose derivatives such as carboxymethylcellulose and
hydroxypropyl
methylcellulose. In one aspect, gels include single phase and double phase
gels.
[0142] In one aspect, a disclosed topical formulation can be formulated as a
jelly. In one aspect,
jellies are water-soluble bases typically prepared from natural gums such as
tragacanth, pectin,
alginate and boroglycerin or from synthetic derivatives of natural substances
such as
methylcellulose and carboxymethylcellulose.
[0143] In some aspects, a disclosed topical formulation can be formulated as a
lotion or
liniment. Examples of lotions include, but are not limited to, hand lotions,
face lotions and body
lotions. Lotions can comprise alcohols such as ethyl alcohol, antiseptics,
emollients and
hemostypic substances. In another aspect, lotions comprise extract of
witchhazel, menthol,
glycerin, boric acid, alum, potassium oxyquinoline; sulfate and chloroform.
[0144] In some aspects, a disclosed topical formulation can be formulated as a
solution. In an
aspect, solvents used to prepare solutions include, but are not limited to,
water, ethyl alcohol
and propylene glycol.
[0145] In another aspect, a disclosed topical formulation can be formulated as
an emulsion. In
some aspects, emulsions include, but are not limited to, water-in-oil, oil-in-
water, water-in-oil-in-
water and oil-in-water-in-oil.
[0146] In one aspect, a disclosed topical formulation can be formulated as a
suspension. In
some aspects, suspensions include, but are not limited to, flocculated and
deflocculated
suspensions.
[0147] In some aspects, a disclosed topical formulation can be formulated in
the form of an
aerosol. In one aspect, topical aerosols comprise hydrocarbons (propane,
butane and
isobutene), and compressed gases such as nitrogen, carbon dioxide and nitrous
oxide.
[0148] In some aspects, a disclosed topical formulation can comprise a healing
ointment such
as Aquaphor . See, U.S. Pat. No. 7,976,854 to Hattendori et al.
[0149] In some aspects the therapeutic composition can be formulated with
VersaBase Cream,
VersaBase Foam ,VersaBase Gel, VersaBase Lotion, or VersaBase Shampoo.
Date Recue/Date Received 2023-08-18
[0150] In some aspects, a disclosed topical formulation can be formulated as a
spot-on
formulation. See, U.S. Pat. No. 7,531,186 to Boeckh et al.. In one aspect, the
topical formulation
comprises the therapeutic composition, a liquid carrier vehicle and optionally
a crystallization
inhibitor. In some aspects, the liquid carrier vehicle comprises a solvent and
a cosolvent
wherein the solvent is selected from the group consisting of acetone,
acetonitrile, benzyl
alcohol, butyl diglycol, dimethylacetamide, dimethylformamide, dipropylene
glycol n-butyl ether,
ethylene glycol monoethyl ether, monomethylacetamide, di propylene glycol
monomethyl ether,
liquid polyoxyethylene glycols, propylene glycol, 2-pyrrolidone, in particular
N-methylpyrrolidone,
diethylene glycol monoethyl ether, ethylene glycol, diethyl phthalate fatty
acid esters, such as
the diethyl ester or diisobutyl adipate, and a mixture of at least two of
these solvents and the
cosolvent is selected from the group consisting of ethanol, isopropanol or
methanol; and
optionally a crystallization inhibitor selected from the group consisting of
an anionic surfactant, a
cationic surfactant, a non-ionic surfactant, an amine salt, an amphoteric
surfactant or
polyvinylpyrrolidone, polyvinyl alcohols, copolymers of vinyl acetate and
vinylpyrrolidone,
polyethylene glycols, benzyl alcohol, mannitol, glycerol, sorbitol,
polyoxyethylenated sorbitan
esters; lecithin, sodium carboxymethylcellulose, and acrylic derivatives, or a
mixture of these
crystallization inhibitors.
[0151] In certain aspects, a disclosed topical formulation comprises: a
disclosed therapeutic
composition, a pharmaceutically acceptable dipolar aprotic solvent or an acid;
and a
pharmaceutically acceptable aqueous secondary solvent. See, U.S. Pat. No.
6,844,004 to
Anderson. In some aspects, the acid is a carboxylic acid and is exemplified by
acetic acid. In
other aspects, the acid is hydrochloric acid. In some aspects, the aqueous
secondary solvent is
a surfactant. Surfactants are well known in the art and are organic lipid
compounds that arc
normally produced by the lung tissue and help with the opening of the alveolar
constrictions
during breathing. Surfactants are also commercially available. In still other
aspects the aqueous
secondary solvent is an aqueous lipid emulsion. The aqueous lipid emulsion can
comprise a
lipid component that includes at least one vegetable oil and at least one
fatty acid. Such a lipid
component can comprise at least about 5% by weight soybean oil and at least
about 50% by
weight fatty acids. In some aspects, the lipids in the composition are
preferably present in a
form other than liposomes, for example, at least about 50% by weight of the
lipid is not in the
form of liposomes, more preferably a least about 75%, and most preferably at
least about 95%.
In other aspects the secondary solvent can be water, a saline solution, or a
dextrose solution. In
some aspects, the composition further comprises an ointment and/or a cream
base. The
ointment base can comprise one or more of petrolatum, mineral oil, ceresin,
lanolin alcohol,
61
Date Recue/Date Received 2023-08-18
panthenol, glycerin, bisabolol, cocoa butter and the like. The ointment or
cream can be any
commonly known commercially available ointments or creams such as AquaphorTM
or
Eucerin TM.
[0152] In various aspects, the disclosed topical formulations can further
comprise additional
ingredients that may be provided in order to facilitate scar reduction, such
as but not limited to:
levocetirizine, pentoxyifylline, gabapentin, tranilast, vitamin E, Emu Oil,
salicylic acid, tretinoin
(retinoic acid), or combinations thereof. Levocetirizein is an antihistamine
used to decrease the
itching associated with healing skin. During the normal healing response mast
cells play a vital
role. It has been found that in the formation of some keloid and hypertrophic
scars there is an
abnormally high amount of mast cells involved. The mast cells can release
histamine causing
the healing skin to itch. Levocetririzine will decrease collagen production at
higher topical
concentrations. Pentoxyifylline, which is a blood viscosity reducer agent and
acts to decreases
collagen production. Gabapentin, which is an inhibition of excitatory
neurotransmitters and
decreases pain caused by firing neurons. Tranilast, which is an anti-allergic
and may be an
indication for keloid and hypertrophic scar. Vitamin E, which promotes skin
elasticity thus
minimizing the tissue tearing. Emu Oil, which is derived from emu fat and
claims to have anti-
inflammatory and skin penetrating properties. Salicylic Acid, which is a
peeling agent for the
treatment of acne, as it removes intercellular lipids that are covalently
linked to the cornified
envelope surrounding cornified epitheliod cells. Tretinoin (retinoic acid),
which is a metabolite of
vitamin A (retinal) and responsible for most of the activity of vitamin A and
is used for acne
treatment, anti-wrinkle, and stretch marks.
[0153] In various aspects, the disclosed topical formulations can comprise a
preservative. As
used herein, the terms "preservative system" or "preservatives" include all
preservatives
approved for use in pharmaceutical, food and beverage compositions including,
without
limitation, such known chemical preservatives as benzoates including sodium,
calcium, and
potassium benzoate, sorbates including sodium, calcium, and potassium sorbate,
citrates
including sodium citrate and potassium citrate, polyphosphates including
sodium
hexametaphosphate (SHMP), and mixtures thereof, and antioxidants such as
ascorbic acid,
EDTA, BHA, BHT, TBHQ, dehydroacetic acid, dimethyldicarbonate, ethoxyquin,
heptylparaben,
and combinations thereof. Preservatives can be used in amounts not exceeding
mandated
maximum levels. In still another aspect, preservatives include antimicrobials
such as
benzalkonium chloride, benzoic acid, benzyl alcohol, bronopol, chlorhexidine,
chlorocresol,
imidazolidinyl urea, paraben esters, phenol, phenoxyethanol, potassium
sorbate, and sorbic
62
Date Recue/Date Received 2023-08-18
acid. Preservatives also include antioxidants such as a-tocopherol, ascorbic
acid, ascorbyl
palmitate, butylated hydroxyanisole, sodium ascorbate, and sodium
metabisulfite.
[0154] In various aspects, the disclosed formulations can optionally further
comprise an
additional ingredient, which may be an inactive ingredient or an inactive
ingredient. In a further
aspect, an optional additional ingredient can be caffeine, saw palmetto
extract, or combinations
thereof.
[0155] In some aspects, the disclosed formulations can optionally comprise
caffeine present in
an amount of from about 0.0001 wt% to about 0.010 wt%. In a further aspect,
the disclosed
formulations can optionally comprise caffeine present in an amount of from
about 0.001 wt% to
about 0.007 wt%. In a still further aspect, the disclosed formulations can
optionally comprise
caffeine present in an amount of from about 0.001 wt% to about 0.005 wt%. In a
yet further
aspect, the disclosed formulations can optionally comprise caffeine present in
an amount of
from about 0.001 wt% to about 0.003 wt%. In various aspects, the disclosed
formulations can
optionally comprise caffeine present in an amount of about 0.0001 wt%, about
0.0002 wt%,
about 0.0003 wt%, about 0.0004 wt%, about 0.0005 wt%, about 0.0006 wt%, about
0.0007 wt%,
about 0.0008 wt%, about 0.0009 wt%, about 0.0010 wt%, about 0.0011 wt%, about
0.0012 wt%,
about 0.0013 wt%, about 0.0014 wt%, about 0.0015 wt%, about 0.0016 wt%, about
0.0017 wt%,
about 0.0018 wt%, about 0.0019 wt%, about 0.0020 wt%, about 0.0021 wt%, about
0.0022 wt%,
about 0.0023 wt%, about 0.0024 wt%, about 0.0025 wt%, about 0.0026 wt%, about
0.0027 wt%,
about 0.0028 wt%, about 0.0029 wt%, about 0.0030 wt%, about 0.0031 wt%, about
0.0032 wt%,
about 0.0033 wt%, about 0.0034 wt%, about 0.0035 wt%, about 0.0036 wt%, about
0.0037 wt%,
about 0.0038 wt%, about 0.0039 wt%, about 0.0040 wt%, about 0.0041 wt%, about
0.0042 wt%,
about 0.0043 wt%, about 0.0044 wt%, about 0.0045 wt%, about 0.0046 wt%, about
0.0047 wt%,
about 0.0048 wt%, about 0.0049 wt%, about 0.0050 wt%, about 0.0051 wt%, about
0.0052 wt%,
about 0.0053 wt%, about 0.0054 wt%, about 0.0055 wt%, about 0.0056 wt%, about
0.0057 wt%,
about 0.0058 wt%, about 0.0059 wt%, about 0.0060 wt%, about 0.0061 wt%, about
0.0062 wt%,
about 0.0063 wt%, about 0.0064 wt%, about 0.0065 wt%, about 0.0066 wt%, about
0.0067 wt%,
about 0.0068 wt%, about 0.0069 wt%, about 0.0070 wt%, about 0.0071 wt%, about
0.0072 wt%,
about 0.0073 wt%, about 0.0074 wt%, about 0.0075 wt%, about 0.0076 wt%, about
0.0077 wt%,
about 0.0078 wt%, about 0.0079 wt%, about 0.0080 wt%, about 0.0081 wt%, about
0.0082 wt%,
about 0.0083 wt%, about 0.0084 wt%, about 0.0085 wt%, about 0.0086 wt%, about
0.0087 wt%,
about 0.0088 wt%, about 0.0089 wt%, about 0.0090 wt%, about 0.0091 wt%, about
0.0092 wt%,
about 0.0093 wt%, about 0.0094 wt%, about 0.0095 wt%, about 0.0096 wt%, about
0.0097 wt%,
63
Date Recue/Date Received 2023-08-18
about 0.0098 wt%, about 0.0099 wt%, about 0.010 wt%; or any range encompassed
by the
foregoing values; or any combination of the foregoing values.
[0156] In some aspects, the disclosed formulations can optionally comprise saw
palmetto
extract present in an amount of from about 0.01 wt% to about 50 wt%. The saw
palmetto extract
can be any suitable nutraceutical or cosmeceutical grade saw palmetto extract.
In a further
aspect, the disclosed formulations can optionally comprise caffeine present in
an amount of
from about 0. 1 wt% to about 30 wt%. In a still further aspect, the disclosed
formulations can
optionally comprise caffeine present in an amount of from about 1 wt% to about
10 wt%. In a yet
further aspect, the disclosed formulations can optionally comprise caffeine
present in an amount
of from about 1 wt% to about 8 wt%. In various aspects, the disclosed
formulations can
optionally comprise caffeine present in an amount of about 0.01 wt%, about
0.02 wt%, about
0.03 wt%, about 0.04 wt%, about 0.05 wt%, about 0.06 wt%, about 0.07 wt%,
about 0.08 wt%,
about 0.09 wt%, about 0.10 wt%, about 0.11 wt%, about 0.12 wt%, about 0.13
wt%, about 0.14
wt%, about 0.15 wt%, about 0.16 wt%, about 0.17 wt%, about 0.18 wt%, about
0.19 wt%, about
0.20 wt%, about 0.21 wt%, about 0.22 wt%, about 0.23 wt%, about 0.24 wt%,
about 0.25 wt%,
about 0.26 wt%, about 0.27 wt%, about 0.28 wt%, about 0.29 wt%, about 0.30
wt%, about 0.31
wt%, about 0.32 wt%, about 0.33 wt%, about 0.34 wt%, about 0.35 wt%, about
0.36 wt%, about
0.37 wt%, about 0.38 wt%, about 0.39 wt%, about 0.40 wt%, about 0.41 wt%,
about 0.42 wt%,
about 0.43 wt%, about 0.44 wt%, about 0.45 wt%, about 0.46 wt%, about 0.47
wt%, about 0.48
wt%, about 0.49 wt%, about 0.50 wt%, about 0.51 wt%, about 0.52 wt%, about
0.53 wt%, about
0.54 wt%, about 0.55 wt%, about 0.56 wt%, about 0.57 wt%, about 0.58 wt%,
about 0.59 wt%,
about 0.60 wt%, about 0.61 wt%, about 0.62 wt%, about 0.63 wt%, about 0.64
wt%, about 0.65
wt%, about 0.66 wt%, about 0.67 wt%, about 0.68 wt%, about 0.69 wt%, about
0.70 wt%, about
0.71 wt%, about 0.72 wt%, about 0.73 wt%, about 0.74 wt%, about 0.75 wt%,
about 0.76 wt%,
about 0.77 wt%, about 0.78 wt%, about 0.79 wt%, about 0.80 wt%, about 0.81
wt%, about 0.82
wt%, about 0.83 wt%, about 0.84 wt%, about 0.85 wt%, about 0.86 wt%, about
0.87 wt%, about
0.88 wt%, about 0.89 wt%, about 0.90 wt%, about 0.91 wt%, about 0.92 wt%,
about 0.93 wt%,
about 0.94 wt%, about 0.95 wt%, about 0.96 wt%, about 0.97 wt%, about 0.98
wt%, about 0.99
wt%, about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4
wt%, about 1.5
wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2.0
wt%, about 2.1
wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6
wt%, about 2.7
wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%, about 3.2
wt%, about 3.3
wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%, about 3.8
wt%, about 3.9
wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%, about 4.4
wt%, about 4.5
64
Date Recue/Date Received 2023-08-18
wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%, about 5.0
wt%, about 5.1
wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%, about 5.6
wt%, about 5.7
wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%, about 6.2
wt%, about 6.3
wt%, about 6.4 wt%, about 6.5 wt%, about 6.6 wt%, about 6.7 wt%, about 6.8
wt%, about 6.9
wt%, about 7.0 wt%, about 7.1 wt%, about 7.2 wt%, about 7.3 wt%, about 7.4
wt%, about 7.5
wt%, about 7.6 wt%, about 7.7 wt%, about 7.8 wt%, about 7.9 wt%, about 8.0
wt%, about 8.1
wt%, about 8.2 wt%, about 8.3 wt%, about 8.4 wt%, about 8.5 wt%, about 8.6
wt%, about 8.7
wt%, about 8.8 wt%, about 8.9 wt%, about 9.0 wt%, about 9.1 wt%, about 9.2
wt%, about 9.3
wt%, about 9.4 wt%, about 9.5 wt%, about 9.6 wt%, about 9.7 wt%, about 9.8
wt%, about 9.9
wt%, about 10 wt%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%,
about 15 wt%,
about 16 wt%, about 17 wt%, about 18 wt%, about 19 wt%, about 20 wt%, about 21
wt%, about
22 wt%, about 23 wt%, about 24 wt%, about 25 wt%, about 26 wt%, about 27 wt%,
about 28
wt%, about 29 wt%, about 30 wt%, about 31 wt%, about 32 wt%, about 33 wt%,
about 34 wt%,
about 35 wt%, about 36 wt%, about 37 wt%, about 38 wt%, about 39 wt%, about 40
wt%, about
41 wt%, about 42 wt%, about 43 wt%, about 44 wt%, about 45 wt%, about 46 wt%,
about 47
wt%, about 48 wt%, about 49 wt%, about 50 wt%; or any range encompassed by the
foregoing
values; or any combination of the foregoing values.
[0157] In various aspects, the disclosed topical formulations can further
comprise conventional
cosmetic adjuvants, such as dyes, pacifiers (e.g., titanium dioxide),
pigments and fragrances.
[0158] In various aspects, the disclosed topical formulations can further
comprise a safe and
effective amount of a penetration enhancing (or reducing) agent. By "safe and
effective amount"
is meant an amount sufficient to enhance (or reduce) the penetration of the
disclosed
therapeutic compositions extracts into the skin, but not so much as to cause
any side effects or
skin reactions. Penetration enhancers can be provided in amounts from about 1%
to about 10%
of the topical formulation.
[0159] In a further aspect, exemplary skin penetration enhancers include
sulfoxides such as
dimethylsulfoxide (DMSO) and the like; cyclic amides such as 1-
dodecylazacycloheptane-2-one
(AZONE, a registered trademark of Nelson Research, Inc.) and the like; amides
such as N,N-
dimethyl acetamide (DMA) N,N-diethyl toluamide, N,N-dimethyl formamide, N,N-
dimethyl
octamide, N,N-dimethyl decamide, and the like; pyrrolidone derivatives such as
N-methy1-2-
pyrrolidone, 2-pyrrolidone, 2-pyrrolidone-5-carboxylic acid, N-(2-
hydroxyethyl)-2-pyrrolidone or
fatty acid esters thereof, 1-laury1-4-methoxycarbony1-2-pyrrolidone, N-
tallowalkylpyrrolidones,
and the like; polyols such as propylene glycol, ethylene glycol, polyethylene
glycol, dipropylene
Date Recue/Date Received 2023-08-18
glycol, glycerol, hexanetriol, and the like; linear and branched fatty acids
such as oleic, linoleic,
lauric, valeric, heptanoic, caproic, myristic, isovaleric, neopentanoic,
trimethyl hexanoic,
isostearic, and the like; alcohols such as ethanol, propanol, butanol,
octanol, oleyl, stearyl,
linoleyl, and the like; anionic surfactants such as sodium laurate, sodium
lauryl sulfate, and the
like; cationic surfactants such as benzalkonium chloride,
dodecyltrimethylammonium chloride,
cetyltrimethylammonium bromide, and the like; non-ionic surfactants such as
the propoxylated
polyoxyethylene ethers, e.g., Poloxamer 231, Poloxamer 182, Poloxamer 184, and
the like, the
ethoxylated fatty acids, e.g., Tween 20, Myrj 45, and the like, the sorbitan
derivatives, e.g.,
Tween 40, Tween 60, Tween 80, Span 60, and the like, the ethoxylated alcohols,
e.g.,
polyoxyethylene (4) lauryl ether (Brij 30), polyoxyethylene (2) oleyl ether
(Brij 93), and the like,
lecithin and lecithin derivatives, and the like; the terpenes such as D-
limonene, a-pinene, p-
carene, a-terpineol, carvol, carvone, menthone, limonene oxide, a-pinene
oxide, eucalyptus oil,
and the like. Also suitable as skin penetration enhancers are organic acids
and esters such as
salicyclic acid, methyl salicylate, citric acid, succinic acid, and the like.
[0160] In various aspects, the disclosed topical formulations can be applied
using a vacuum
actuated applicator. In some aspects, the vacuum actuated applicator is
designed to provide
blocking of UV light and minimize oxidation.
Methods of Using the Disclosed Formulations
[0161] In various aspects, the disclosed topical formulations can be applied
to the scalp and/or
hair once per day or in multiple applications applied in various fractions of
a 24 hour period. In a
further aspect, disclosed topical formulations can be applied to the scalp
and/or hair once per
day, twice per day, three times per day, four times per day, five times per
day, or six times per
day.
[0162] Now having described the aspects of the present disclosure, in general,
the following
Examples describe some additional aspects of the present disclosure. While
aspects of the
present disclosure are described in connection with the following examples and
the
corresponding text and figures, there is no intent to limit aspects of the
present disclosure to this
description. On the contrary, the intent is to cover all alternatives,
modifications, and equivalents
included within the spirit and scope of the present disclosure.
EXAMPLES
[0163] The following examples are put forth so as to provide those of ordinary
skill in the art
with a complete disclosure and description of how the compounds, compositions,
articles,
66
Date Recue/Date Received 2023-08-18
devices and/or methods claimed herein are made and evaluated, and are intended
to be purely
exemplary of the disclosure and are not intended to limit the scope of what
the inventors regard
as their disclosure. Efforts have been made to ensure accuracy with respect to
numbers (e.g.,
amounts, temperature, etc.), but some errors and deviations should be
accounted for. Unless
indicated otherwise, parts are parts by weight, temperature is in C or is at
ambient temperature,
and pressure is at or near atmospheric.
[0164] Example 1. An exemplary disclosed formulation was prepared comprising:
(a) active
ingredients: azelaic acid .325 wt%, minoxidil 15 wt%, finasteride .2 wt%, and
dutasteride .01%
w/v%; and (b) compound components: ethoxy Di-Glycol (6 ml per 100 gm of final
weight),
specific gravity = 1.05; propylene glycol (3.5 ml per 100 gm of final weight),
specific gravity =
1.1; VersaBase Gel (11 gm per 100 gm of final weight); heavy cream base (22.5
gm per 100
gm of final weight); and silicone base (27.75 gm per 100 gm of final weight).
The silicone base
used was either Pracasile (PCCA) or Scar Care Base Enhanced (Letco Medical).
[0165] The subject noted that the exemplary formulation did not have the oily
viscosity
associated with conventional topical formulations that resulted in a wetted
hair look when
applied. The subject further noted that the exemplary formulation appeared to
have an
immediate nourishing effect on their hair with almost immediate cessation of
hair loss stopped
and growth of new dark thicker hair with a healthy looking appearance.
Moreover, it was noted
that it was not necessary to apply the cream twice a day as one application
daily was found to
be sufficient. The subject further observed that conventional formulations
often were associated
with scalp itching after about 12 hours. In contrast, the exemplary
formulation was not
associated with scalp itching. Moreover, the exemplary formulation appeared to
provide a
healthy scalp with little or no appearance of flaking skin.
[0166] Example 2. An exemplary disclosed formulation was prepared comprising:
(a) active
ingredients: azelaic acid .325 wt%, minoxidil 15 wt%, finasteride .2 wt%, and
dutasteride .01%
w/v%; (b) other ingredients: caffeine 0.0025 wt%; and (c) compound components:
ethoxy di-
glycol (6 ml per 100 gm of final weight), specific gravity = 1.05; propylene
glycol (3.5 ml per 100
gm of final weight), specific gravity = 1.1; VersaBase Gel (PCCA; 10 gm per
100 gm of final
weight); HRT cream base (Letco Medical; 21.5 gm per 100 gm of final weight);
and silicone
base (26.75 gm per 100 gm of final weight). The silicone base used was either
Pracasil
(PCCA) or Scar Care Base Enhanced (Letco Medical).
[0167] The subject noted similar results as obtained in Example 1. In
particular, the subject note
that the exemplary formulation had the following characteristics: (a) the
exemplary formulation
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Date Recue/Date Received 2023-08-18
stays in place on the scalp and does not run off onto forehead or cheek areas;
(b) the
exemplary formulation does not require two applications per day, one is enough
to last 24 or
more hours before reapplication; (c) the viscosity of the exemplary
formulation provides for
extended contact of the active ingredients with scalp; and (d) the exemplary
formulation appears
to provide scalp healing benefits such as improved overall scalp health,
decrease or complete
itch relief, increased blood flow, and improved hair growth. In contrast,
conventionally available
formulations having 5-15 wt% minoxidil were found by the subject to be quite
oily, which allowed
it to better stay in place on the scalp, but it transferred onto the hair it
made the hair look like it
was oily with an extended period of time required for the conventional
formulation to dry to the
point that the hair had a more natural, non-oily appearance.
[0168] It should be emphasized that the above-described aspects of the present
disclosure are
merely possible examples of implementations set forth for a clear
understanding of the
principles of the disclosure. Many variations and modifications may be made to
the above-
described aspect(s) without departing substantially from the spirit and
principles of the
disclosure. All such modifications and variations are intended to be included
herein within the
scope of this disclosure and protected by the following claims.
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Date Recue/Date Received 2023-08-18
